bims-engexo Biomed News
on Engineered exosomes
Issue of 2026–06–14
sixty-six papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Exosome engineering: The promise and peril of targeted delivery for treating ocular diseases.
  2. Engineered Exosomes Deliver miR-370 Inhibitor to Regulate DNAJB1 and Synergize With miR-25 in Improving SCA3 Mice Behavior and Neuropathology.
  3. Exosome Therapy: A Novel Investigational Approach in Acute Myocardial Infarction.
  4. Therapeutic exosomes in cancer: efficacy and safety perspectives.
  5. DNA hydrogel-delivered hypoxic exosomes alleviate radiation-induced skin injury by stabilizing AKT.
  6. Macrophage PSRC1 attenuates atherosclerosis via extracellular vesicle-mediated MBD2 delivery to induce PCSK9 promoter methylation in hepatocytes.
  7. Rebuilding the degenerative disc microenvironment: mesenchymal stem cells, exosomes, and bioengineered scaffolds.
  8. CHP/MMP2 dual-targeting soft mesoporous organosilica nanoparticles loaded with losartan for modulating cardiac fibrosis.
  9. Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection.
  10. BMSC-derived exosomal miR-27a-3p ameliorates osteoarthritis via dual regulation of chondrocyte protection and macrophage M1 polarization through TXNIP/NLRP3 signaling.
  11. Dysregulation of exosomal miRNAs in A2 astrocytes under oxygen-glucose deprivation is associated with neuronal pyroptosis: a role for miR-139-5p in targeting NLRP3.
  12. An integrated nano-delivery platform via baicalein-loaded polydopamine-MOF for enhanced neuroprotection against retinal ischemia reperfusion injury.
  13. Enhancing cancer vaccine efficacy via electrostatic engineering of an FcγR-targeted protein.
  14. Nanoparticle-mediated intracellular delivery of biomolecules to plants: From mechanistic insights to translational challenges.
  15. Innovative mucosal nanocarrier systems for enhanced immune response against respiratory pathogens.
  16. Macrophage immunometabolism in stroke: a view from single-cell and nano technologies.
  17. Isoquercitrin-loaded adipose-derived stem cell exosomes synchronize immunomodulation and neurovascular remodeling to accelerate spinal cord regeneration.
  18. Exosomes from adipose-derived stem cells preconditioned with 650- or 810-nm photobiomodulation enhance cutaneous wound healing in rats.
  19. Engineering peroxisomal cofactor systems in Saccharomyces cerevisiae for enhanced biosynthesis of α-humulene.
  20. Targeting the IKKα/NF-κB Axis with SGEC-Derived Exosomal miR-23b-3p Rebalances Treg/Th17 Immunity in Sjögren's Syndrome.
  21. Engineering human PEG10-based nanoparticles for RNA self-packaging, delivery and cancer therapy.
  22. Exosomes From Adipose-Derived Mesenchymal Stem Cells: A New Prospective Therapy of Diabetic Foot Ulcer.
  23. A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment.
  24. The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System.
  25. Tumor-derived extracellular vesicles: From biogenesis and molecular composition to translational therapeutics.
  26. Identification, Characterization, and Engineering of a Novel 3-Ketosteroid-Δ1-Dehydrogenase.
  27. The Role of Exosomes in Bone Metastasis and Bone Tissue Engineering: Molecular Mechanisms and Therapeutic Opportunities.
  28. Membrane-Anchoring Naphthalimide-Based Aggregation-Induced Emission Photosensitizers for NIR Fluorescence Imaging and Photodynamic Elimination of Multidrug-Resistant Bacteria.
  29. Polyethylene glycol-maleimide amphiphilic carboxymethyl-hexanoyl chitosan enables cadherin-11-targeted hyaluronan synthase 2 delivery and hyaluronan biosynthesis in osteoarthritis.
  30. Orbital hybridization-mediated nanozymes reverse cellular senescence for aged bone regeneration.
  31. Peptides as programmable molecular scaffolds: from chemical synthesis and engineering to translational medicine.
  32. Serum starvation drives ALIX-dependent extracellular vesicle biogenesis and determines tumor progression.
  33. Magnetically guided biohybrid microrobots with multimodal locomotion for barrier penetration and multifunctional tumor treatment.
  34. CEN-Display: Construction and optimization of a surface display system in Saccharomyces cerevisiae CEN.PK2-1C.
  35. Enhanced ocular delivery of tacrolimus via cationic nanoliposomes: Mitigating inflammation and rebalancing Th17/Treg responses in dry eye disease.
  36. Emerging paradigms in nanostructured targeted drug delivery systems.
  37. Lyophilized bacteria-infected tumor cells for targeted immunotherapy of lung metastases and associated fibrosis.
  38. Engineered Lactococcus lactis for Oral Delivery of an Antimicrobial Peptide against Enterotoxigenic Escherichia coli in Weaned Piglets.
  39. CRISPR application in hematological disorders: from bench to bedside.
  40. Cell therapy comparison of dental pulp stem cells, hepatocytes, and their exosomes for liver fibrosis treatment in rats.
  41. A closed-loop myocardial infarction theranostic platform activated by macrophage-derived nitric oxide and acidic microenvironment.
  42. CAR-T Cell-Derived Exosomes and Cancer Immunotherapy: Advancing Production and Delivery Through Biofabrication.
  43. Peptide-MHC-targeted engineered virus-like particles enable selective priming and gene editing of tumor-specific T cells.
  44. Chitosan-hyaluronic acid engineered polycaprolactone nanoparticles enhance curcumin antiplasmodial activity and preserve blood-brain barrier integrity.
  45. 3D-printed PCL/nHA/SA/COL loaded with M2 macrophage-derived exosomes alleviates the senescence of bone marrow mesenchymal stem cells.
  46. Surface Functionalization of 3D-Printed Porous Ti-6Al-4V Scaffolds with PDA‑mHA-Col I Composite Coating Drives Macrophage Polarization toward the M2 Phenotype and Promotes Immunomodulation: An In Vitro Study.
  47. Ag-Based Schottky-Engineered MOF Sonosensitizers Delivered via Dissolvable Microneedles for Sonodynamic Biofilm Eradication and Wound Healing.
  48. Hierarchical Design Synergizing Local Dynamics Optimization and Global Rigidification Unlocks the Catalytic Potential of d-Erythrose-4-phosphate Dehydrogenase.
  49. Immunoengineering in the field of tendon and bone regeneration: immunomodulatory biomaterials, delivery platforms, and preclinical models for chronic diseases.
  50. Magnetic enrichment and enabled cascade amplification for ultrasensitive SPR analysis of PD-L1+ exosomes.
  51. Molecular glue degraders versus PROTACs: a novel paradigm in targeted protein degradation.
  52. Estimation of gut microbiome motif associated with active tuberculosis - A case control study.
  53. Oral microbiota member Neisseria elongata exosomes-Cassia fistula association targets PTEN/AKT/IL10/IL1β/BAX/BCL-2 signaling pathway in pancreatic cancer immunotherapy.
  54. Potential Role of Exosomes in the Pathogenesis, Diagnosis, and Treatment of Ovarian Cancer.
  55. A newly developed eGFP-traceable recombinant rhesus lymphocryptovirus, a tool to study viral infection and replication in vitro and ex vivo, confirms gp350 as key for viral entry.
  56. Engineered protein nanoclusters reduce liver fibrosis and hepatocellular carcinoma in mice models.
  57. Multivalent Aptamers: Contemporary Engineering Strategies and Biomedical Applications.
  58. Familial Hypercholesterolemia Combined With Sitosterolemia.
  59. Folate-Targeted Liposomal Delivery of a Ru(II)-Based Photosensitizer for Photodynamic Tumor Therapy via Pyroptosis Induction.
  60. AI-assisted label-free single-particle analysis of milk-derived extracellular vesicles enabled by nanotweezers.
  61. Engineering a PD-L1-sensing synthetic receptor for programmable macrophage response.
  62. Closed-loop iron chelate recycling via molecularly imprinted hydrogels suppresses ferroptosis.
  63. Colon-targeted alginate/chitosan microspheres for co-delivery of synbiotics and nanozymes ameliorate inflammatory bowel disease.
  64. Engineering nanoplatforms for autoimmune treatment: From synthetic strategies to bioinspired designs.
  65. Parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation patterns and autism-like behaviors in offspring.
  66. Bio-inspired stearic acid functionalized polylactic acid nanofibers with nanodome architecture for enhanced oil-water separation.
  1. Tissue Cell. 2026 Jun 04. pii: S0040-8166(26)00358-7. [Epub ahead of print]103 103664
    Exosome engineering: The promise and peril of targeted delivery for treating ocular diseases.
    Elham Sharif, Nader Hashemi, Fatemeh Eskandari, Forough Shams, Mahmood Rekabgardan.
      In the absence of acceptable cures for ocular diseases, stem cells and their paracrine agents, including exosomes, have become a promising therapeutic approaches. Exosomes are lipid spherical bilayer-encased particles and the smallest subtype of extracellular vehicles (EVs) that are secreted by cells to facilitate intercellular communication in the form of lipids, proteins, mRNAs, and small RNAs. Recent advances in exosome-based therapeutics have witnessed unique opportunities for treating ocular diseases, including autoimmune diseases, traumatic diseases, chorioretinal diseases, and uveal melanoma. Many studies demonstrated that exosomes, in particular, bioengineered exosomes have an impressive effect on target cells. The utilization of exosomes as delivery vectors to encapsulate both therapeutic genes and drugs, surface modification, and encapsulation by biomaterial could yield higher efficacy and avoid unnecessary immune responses. Several studies demonstrated the therapeutic effects of stem cells are due to engineered exosomes. However, exosome-based therapies also show some potential ocular risks. In this review, we first present the origins and general introduction to exosomes. We then provide an overview of the surface modification of MSC-derived exosomes, drug-loaded exosomes, bioengineering, and biomaterial-based exosomes. Eventually, we discussed available applications, their potential risks, and proposed future perspectives to address the translation and underlying issues related to ocular disease.
    Keywords:  Bioengineering exosomes; Drug loading exosomes; MSCs; Ocular disease
    DOI:  https://doi.org/10.1016/j.tice.2026.103664
  2. FASEB J. 2026 Jun 15. 40(11): e72036
    Engineered Exosomes Deliver miR-370 Inhibitor to Regulate DNAJB1 and Synergize With miR-25 in Improving SCA3 Mice Behavior and Neuropathology.
    Ziyi Zhang, Shuguang Gao, Lixia Qin, Miao He.
      Spinocerebellar ataxia type 3 (SCA3), the most common inherited ataxia, lacks effective therapies. Current microRNA (miRNA) approaches directly targeting ataxin-3 (ATXN3) mRNA risk reducing essential wild-type ATXN3, a key regulator of proteostasis and various signaling pathways. Consequently, developing neuron-targeted, noninvasive miRNA delivery strategies that employ alternative mechanisms is critical for SCA3. In this study, we engineered rabies virus glycoprotein (RVG)-modified exosomes to deliver miR-370 inhibitors to the brains of SCA3 mice, thereby upregulating the molecular chaperone DnaJ homolog subfamily B member 1 (DNAJB1) to promote clearance of mutant ATXN3. Systemic administration of RVG-exosomes carrying miR-370 inhibitors led to increased DNAJB1 expression, reduced mutant ATXN3 aggregation, improved neuronal survival, and restored motor coordination in SCA3 mice. Furthermore, combining miR-370 inhibitors with miR-25-a miRNA that directly targets ATXN3 mRNA-synergistically enhanced the reduction of pathogenic ATXN3 and provided greater neuroprotection compared to either therapy alone. These findings support the use of RVG-exosome-mediated miR-370 inhibition as a noninvasive strategy to improve proteostasis in SCA3 and demonstrate its potential in combination with ATXN3 mRNA-targeting miRNAs, offering a promising therapeutic paradigm for SCA3 and similar neurodegenerative disorders.
    Keywords:  exosome; heat shock proteins; microRNA; microRNA inhibitor; spinocerebellar ataxia
    DOI:  https://doi.org/10.1096/fj.202601357RR
  3. Cardiol Rev. 2026 Jun 12.
    Exosome Therapy: A Novel Investigational Approach in Acute Myocardial Infarction.
    Aparna Joshi, Richa Gupta, Tsering Sangdup, Justin Jacob, Anjali Aggarwal.
      Despite major advances in reperfusion therapy and pharmacological management, acute myocardial infarction (AMI) remains one of the leading causes of mortality and morbidity worldwide. Conventional treatment strategies primarily focus on restoring coronary blood flow to ischemic myocardium; however, their ability to regenerate damaged cardiac tissue remains limited. In recent years, exosomes have emerged as a promising cell-free therapeutic approach for cardiac repair following AMI. Exosomes are nanosized extracellular vesicles secreted by various cell types that carry diverse bioactive molecules, including microRNAs, proteins, lipids, and signaling factors, which mediate intercellular communication and regulate multiple biological processes involved in myocardial healing. Emerging experimental and preclinical evidence suggests that exosome-based therapy may attenuate inflammation, reduce cardiomyocyte apoptosis, enhance angiogenesis, modulate immune responses, and promote myocardial regeneration following ischemic injury. Compared with conventional stem cell therapy, exosomes offer several advantages, including lower immunogenicity, reduced risk of tumorigenicity, improved stability, and easier storage and handling. Furthermore, engineered exosomes and targeted delivery systems are being investigated to enhance therapeutic specificity and efficacy in cardiovascular diseases. In addition to their therapeutic potential, circulating exosomes are also being explored as diagnostic and prognostic biomarkers for the early detection and monitoring of AMI. This review highlights the biological characteristics of exosomes, their mechanisms of action in myocardial repair, current experimental and clinical evidence, and future perspectives of exosome-based therapeutics in the management of AMI.
    Keywords:  acute myocardial infarction; exosomes; intranasal; mechanism; therapy
    DOI:  https://doi.org/10.1097/CRD.0000000000001365
  4. RSC Adv. 2026 Jun 02. 16(33): 30633-30648
    Therapeutic exosomes in cancer: efficacy and safety perspectives.
    Rajib Dhar, Ling Shing Wong, Vetriselvan Subramaniyan.
      Extracellular vesicles (EVs) are essential signalling mediators within biological systems, playing a vital role in cell-to-cell communication. In cancer research, exosomes (a subpopulation of EVs that originate from endosomes) have become the most highlighted area of study in the current decade. Tumor-derived exosomes (TEXs) participate in tumor development and cancer progression. They regulate tumor cell growth, immune suppression, angiogenesis, metastasis, epithelial-mesenchymal transition and organ-specific metastasis. The molecular signatures of exosomes, including DNA, RNA, proteins, and lipids, play a crucial role in cancer development and hold significantly promising biomarkers for cancer. Beyond their pathological role, EVs offer a cell-free platform for the development of therapeutic methods for cancer. This phenomenon is having a huge impact compared to cell-based therapy by overcoming several limitations, such as toxicity, high cost, and effectiveness. Multiple therapeutic exosome sources are available, including stem cell-derived exosomes, plant-derived exosomes, immune cell-derived exosomes, and modified exosomes. Compared with conventional cell-based therapies, exosome-based strategies present several advantages, including reduced toxicity, biocompatibility, improved stability, and specificity. Multiple therapeutic exosomes sources are available, including stem cell-derived exosomes, plant cell-derived exosomes, immune cell-derived exosomes, milk-derived exosomes, bacteria-derived exosomes, and modified/engineered exosomes. The therapeutic impact of these exosomes is strongly influenced by multiple factors, such as their cellular origin, heterogeneity, inner cargos, surface charge, surface composition and physicochemical properties. This review discusses the current limitations, key challenges and future perspectives related to exosome-based therapeutics with particular emphasis on the comparative and translational potential of different exosome sources.
    DOI:  https://doi.org/10.1039/d6ra00373g
  5. J Nanobiotechnology. 2026 Jun 10.
    DNA hydrogel-delivered hypoxic exosomes alleviate radiation-induced skin injury by stabilizing AKT.
    Qing Yin, Shihua Deng, Ye Liu, Hui Luo, Shuchen Yuan, Yingdan Fei, Guangchao Xu, Teng Liu, Ting Zhang, Zhongyong Jiang, Kejian Pan, Dongming Wu, Ying Xu.
       BACKGROUND: Radiation-induced skin injury (RISI) is a common and refractory complication during tumor radiotherapy, characterized by radiation stress-induced impairment of keratinocyte viability and regenerative signaling, ultimately leading to delayed skin repair. Recently, hypoxia-preconditioned adipose-derived stem cell-derived exosomes (A-Hexos), a cell-free therapeutic strategy with favorable biocompatibility, has considerable potential in skin injury repair. However, the underlying mechanisms of A-Hexos in the treatment of RISI have not been fully elucidated, and their delivery efficiency and retention capacity at skin injury sites remain suboptimal. In this study, we aimed to enhance the targeted delivery efficiency of exosomes in skin tissues, systematically evaluate the therapeutic effects of A-Hexos in RISI repair, and elucidate the underlying molecular mechanisms.
    RESULTS: In vitro experiments demonstrated that A-Hexos significantly restored the viability, proliferative capacity, and migratory behavior of irradiated keratinocytes (HaCaT). To enhance the local delivery efficiency and tissue retention of exosomes at injured sites in vivo, we constructed a DNA hydrogel-based delivery system loaded with A-Hexos (Gel@A-Hexos), which was engineered through the specific interaction between an exosome membrane protein-specific aptamer (Apt CD63) designed on long DNA strands and the exosomal membrane protein, CD63. In a murine RISI model, Gel@A-Hexos markedly alleviated radiation-induced injury and promoted skin tissue structural reconstruction. Mechanistically, miRNA sequencing revealed that miR-486-5p was significantly enriched in A-Hexos, while proteomic analysis further indicated that Gel@A-Hexos treatment markedly downregulated RNF213 expression and concomitantly upregulated AKT expression in injured skin tissues. Functionally, miR-486-5p delivered by A-Hexos stabilized AKT protein levels by inhibiting RNF213-mediated ubiquitin-dependent AKT degradation, thereby alleviating RISI and promoting tissue repair.
    CONCLUSION: Collectively, this study proposes a long DNA strand-based exosome local delivery hydrogel and elucidates the molecular mechanism by which A-Hexos exert reparative effects on RISI via the miR-486-5p/RNF213/AKT signaling axis, providing new theoretical insights and a potential translational strategy for the precise treatment of RISI.
    Keywords:  DNA hydrogel; Exosomes; Radiation-induced skin injury; miR-486-5p
    DOI:  https://doi.org/10.1186/s12951-026-04653-2
  6. Cell Biosci. 2026 Jun 09.
    Macrophage PSRC1 attenuates atherosclerosis via extracellular vesicle-mediated MBD2 delivery to induce PCSK9 promoter methylation in hepatocytes.
    Tongwei Wu, Hui Huang, Xiaoqian Zhang, Xinyi Feng, Weiming Luo, Lilong Lin, Dan Liu, Hangyu Pan, Shaopeng Wang, Jierong Zhang, Xianyi Zhang, Zhigang Guo, Mengzhuo Yin, Shiping Cao, Yanan Zhang.
       BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by dysregulated lipid metabolism and chronic inflammation. However, the mechanisms governing immune-liver crosstalk in this context remain poorly defined. Proline/serine-rich coiled-coil protein 1 (PSRC1) is a known regulator of cholesterol metabolism, but whether macrophage-derived PSRC1 influences hepatic functions via intercellular communication is unknown.
    METHODS: The relationship between macrophage PSRC1 and hepatic PCSK9 was examined in patients with coronary artery disease and murine models. We employed AAV6-mediated macrophage-specific targeting and whole-body Psrc1⁻/⁻ mice to evaluate cell-type-specific effects. Macrophage-hepatocyte communication was investigated using transwell systems and genetic blockade of EV secretion (sh-Rab27a). The selectivity of EV cargo loading was validated by protease protection assays and TSG101 interaction analysis. In vivo EV tracking (DiI-labeling) and ChIP-qPCR for DNMT recruitment were performed to elucidate the systemic and epigenetic mechanisms.
    RESULTS: Macrophage PSRC1 expression was significantly reduced in atherosclerotic conditions and inversely correlated with hepatic PCSK9 levels. Macrophage-specific PSRC1 depletion alone was sufficient to recapitulate the systemic hypercholesterolemia and accelerated atherosclerosis observed in whole-body knockout models. PSRC1 was found to interact with TSG101 to promote the selective loading of MBD2 into the EV lumen, a process confirmed by protease protection. These MBD2-enriched EVs were preferentially sequestered by the liver after systemic administration. Mechanistically, transferred MBD2 functioned as an epigenetic scaffold, recruiting DNA methyltransferases (DNMT1/3A) to the PCSK9 promoter to drive CpG hypermethylation and transcriptional repression. In vivo, administration of MBD2-enriched EVs significantly reduced hepatic PCSK9 protein, lowered plasma cholesterol, and enhanced plaque stability in ApoE⁻/⁻ mice.
    CONCLUSIONS: Our findings uncover a novel macrophage-liver epigenetic axis where macrophage PSRC1 controls systemic cholesterol homeostasis by regulating the EV-mediated delivery of MBD2. This "Reader-recruits-Writer" mechanism provides a refined understanding of immune-metabolic crosstalk and suggests that engineered EV-based MBD2 delivery represents a promising therapeutic strategy for ASCVD.
    Keywords:  Atherosclerosis; Extracellular vesicles; PSRC1
    DOI:  https://doi.org/10.1186/s13578-026-01598-9
  7. Front Bioeng Biotechnol. 2026 ;14 1802866
    Rebuilding the degenerative disc microenvironment: mesenchymal stem cells, exosomes, and bioengineered scaffolds.
    Dong Guo, Lin Xiao, Hui Li, Ying Pan, Huan Zhang.
      Intervertebral disc degeneration (IVDD) is a leading cause of chronic low back pain, yet current clinical interventions remain largely palliative and fail to restore disc structure and function. While mesenchymal stem cells (MSCs), exosomes, and bioengineered scaffolds have emerged as promising regenerative tools, isolated therapeutic applications often fail to overcome the highly hostile IVDD microenvironment-characterized by severe hypoxia, acidosis, and mechanical overload. This review provides a unique perspective by positioning the "cell-material-molecule" cross-integration as the central paradigm for effective disc regeneration. We critically synthesize how smart biomaterials are engineered to physically match and survive the degenerative niche, thereby providing a resilient sanctuary for MSCs. Concurrently, we highlight how engineered MSCs and their cell-free derivatives (exosomes and regulatory RNAs) synergistically dismantle inflammatory cascades and matrix breakdown. Beyond outlining preclinical and clinical advances, this review deeply analyzes persistent translational bottlenecks-such as cell source standardization, large-scale GMP exosome manufacturing, and long-term scaffold biocompatibility. Ultimately, by outlining the convergence of gene editing, responsive biomaterials, and precision delivery, we define a clear roadmap for transitioning IVDD treatment from palliative symptom management to durable, precision regenerative medicine.
    Keywords:  biomaterials; exosomes; intervertebral disc degeneration; mesenchymal stem cells; regenerative medicine; tissue engineering
    DOI:  https://doi.org/10.3389/fbioe.2026.1802866
  8. Nanomedicine. 2026 Jun 11. pii: S1549-9634(26)00075-4. [Epub ahead of print] 102974
    CHP/MMP2 dual-targeting soft mesoporous organosilica nanoparticles loaded with losartan for modulating cardiac fibrosis.
    Qing Yang, Shilin Zhang, Meng Dang, Cynthia Taub, Christopher Lee, Fen Chen, Zha Teng, Jing Yao.
      Myocardial fibrosis (MF) drives heart failure and arrhythmias, yet drug delivery to injured myocardium is hindered by the dynamic cardiac microenvironment and lack of lesion-specific targeting. Here, we developed a dual-targeted, soft mesoporous organosilica nanoparticles (SMONs) system, which were co-functionalized with a cardiac homing peptide (CHP) and an anti-matrix metalloproteinase 2 antibody (Ab-MMP 2) for the delivery of losartan (LOS). LOS@SMONs-CHP/MMP2 exhibited excellent deformability and outstanding cellular uptake capability. In a murine model of isoproterenol (ISO)-induced myocardial fibrosis, LOS@SMONs-CHP/MMP2 exhibited significantly increased accumulation of fibrosis. In vitro treatment with these nanoparticles potently suppressed cardiac fibroblast activation, proliferation and migration, and markedly reduced collagen deposition and expression of fibrotic markers in vivo. Consequently, cardiac systolic function was substantially improved, outperforming free losartan. Comprehensive biosafety evaluations confirmed minimal cytotoxicity and no acute organ toxicity. This study offering a promising and translatable nano platform for the treatment of cardiac fibrosis.
    Keywords:  Drug delivery; Heart dual-targeted; Myocardial fibrosis; Soft mesoporous organosilica nanoparticles
    DOI:  https://doi.org/10.1016/j.nano.2026.102974
  9. Nat Commun. 2026 Jun 10.
    Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection.
    Jeremy Garb, David W Adams, Eliane Hadas Yardeni, Melanie Blokesch, Rotem Sorek.
      Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based therapies and restricting genetic engineering applications. Here, we employ a de-novo protein design approach to generate proteins that bind and inhibit bacterial defense systems. We show that our synthetically designed proteins block defense, and that phages engineered to encode the synthetic proteins can replicate in cells that express the respective defense system. We further demonstrate that a single phage could be engineered with multiple anti-defense proteins, yielding improved infectivity in bacterial strains carrying multiple defense systems. Finally, we show that plasmids that express synthetic anti-defense proteins can be introduced into bacteria that naturally restrict plasmid transformation. Our approach can broaden host ranges of therapeutic phages and can improve genetic engineering efficiency in strains that are typically difficult to transform.
    DOI:  https://doi.org/10.1038/s41467-026-74301-8
  10. Arch Biochem Biophys. 2026 Jun 08. pii: S0003-9861(26)00173-6. [Epub ahead of print] 110902
    BMSC-derived exosomal miR-27a-3p ameliorates osteoarthritis via dual regulation of chondrocyte protection and macrophage M1 polarization through TXNIP/NLRP3 signaling.
    Liangbin Jiang, Ming Li, Haiyan Wu, Lei Peng.
      Osteoarthritis (OA) is a degenerative joint disorder marked by cartilage degradation and synovial inflammation, for which effective treatments remain limited. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have emerged as promising cell-free therapies due to their immunomodulatory properties. In this study, we investigated whether exosomes from BMSCs overexpressing miR-27a-3p alleviate OA by targeting the TXNIP/NLRP3 axis in both chondrocytes and macrophages. BMSCs were transfected with miR-27a-3p mimics, and exosomes (Exos-miR-27a-3p) were isolated and characterized. Exos-miR-27a-3p were internalized by chondrocytes and directly targeted TXNIP, thereby reversing IL-1β-induced suppression of proliferation, migration, and matrix synthesis, while reducing catabolic factors. In macrophages, Exos-miR-27a-3p inhibited LPS-induced M1 polarization, decreased pro-inflammatory cytokines, and suppressed TXNIP/NLRP3-associated inflammasome activation, as indicated by reduced caspase-1 cleavage, IL-1β maturation/release and ASC speck formation. TXNIP overexpression partially reversed these protective effects. In a mouse model of OA, intra-articular injection of Exos-miR-27a-3p attenuated cartilage degeneration, preserved proteoglycan content, reduced M1 macrophages in synovial tissue, and suppressed TXNIP expression. Collectively, these findings suggest that BMSC-derived exosomal miR-27a-3p alleviates OA through a dual-cell mechanism involving direct chondrocyte protection and macrophage inflammatory reprogramming via the TXNIP/NLRP3 axis.
    Keywords:  BMSC; Exosomes; NLRP3; Osteoarthritis; TXNIP; miR-27a-3p
    DOI:  https://doi.org/10.1016/j.abb.2026.110902
  11. J Orthop Surg Res. 2026 Jun 11.
    Dysregulation of exosomal miRNAs in A2 astrocytes under oxygen-glucose deprivation is associated with neuronal pyroptosis: a role for miR-139-5p in targeting NLRP3.
    Guoliang Ma, Xiaokuan Qin, Bo Xu, Xiongjie Tang, Zhizhuang Wang, Dongsheng Yuan, Renkun Zhao, Penghui Li, Liguo Zhu, He Yin, Bowen Yang, Xin Chen.
       BACKGROUND: A2 astrocyte exosomes are closely associated with neuronal pyroptosis. Reduced expression of miR-139-5p was detected in A2 astrocyte exosomes under oxygen-glucose deprivation (OGD) conditions. We postulate that miR-139-5p intensifies neuroinflammation by modulating the expression of neuronal NLRP3 pyroptosis protein.
    OBJECTIVE: To identify differentially expressed exosomal miRNAs from A2 astrocytes under OGD conditions and to evaluate their potential roles in neuronal pyroptosis.
    METHODS: Administer interleukin-4 (IL-4) to microglia, harvest the supernatant to induce A2 astrocytes, expose them to oxygen deprivation models to isolate exosomes, then co-culture these exosomes with both healthy neurons and neurons subjected to OGD conditions to assess pyroptosis levels in the neurons. Subsequently, execute miRNA sequencing on exosomes from various circumstances to analyze differentially expressed microRNAs and their associated pathways. Finally, the differential targeting relationship between miR-139-5p and NLRP3 was validated using a dual luciferase reporter assay.
    RESULTS: Oxygen-glucose deprivation (OGD) reduced A2 astrocyte viability, with 1 h selected as the optimal duration (p < 0.001). Exosomes from OGD-treated astrocytes were internalized by neurons, decreasing viability (p < 0.001) and increasing pyroptosis-related proteins (p < 0.01). miRNA sequencing identified 133 differentially expressed miRNAs (62 upregulated, 71 downregulated), with miR-139-5p significantly downregulated. Dual-luciferase assays confirmed that miR-139-5p directly targets NLRP3 (p < 0.001).
    CONCLUSIONS: Of five pyroptosis-associated exosomal miRNAs (miR-214-3p, miR-22-5p, miR-139-5p, miR-382-3p, and miR-365-5p), miR-139-5p and miR-382-3p were downregulated under OGD, and miR-139-5p directly targeted NLRP3. Thus, exosomal miRNAs, particularly miR-139-5p, warrant further therapeutic investigation in neurodegenerative diseases, including degenerative cervical myelopathy.
    Keywords:  A2 Astrocyte; Exosomes; Neuronal pyroptosis; Oxygen-glucose deprivation model; miR-139-5p
    DOI:  https://doi.org/10.1186/s13018-026-06966-2
  12. Mater Today Bio. 2026 Jun;38 103239
    An integrated nano-delivery platform via baicalein-loaded polydopamine-MOF for enhanced neuroprotection against retinal ischemia reperfusion injury.
    Xin Liu, Keke Huang, Zhiqing Lin, Min Tang, Qianyi Lin, Wangdu Luo, Jiaguo Yuan, Junlong Yu, Yujie Rao, Peizeng Yang, Lin Xie.
      Retinal ischemia reperfusion injury (RIRI) presents a complex pathological mechanism involving oxidative stress, neuroinflammation, and retinal ganglion cell (RGC) apoptosis, with current therapies limited by their inability to address these multifaceted cascades. To address this challenge, we engineered microenvironment-responsive nanoparticles, pZIF-8@Bai, by encapsulating baicalein (Bai) within a polydopamine-coated zeolitic imidazolate framework (ZIF-8), The pZIF-8@Bai nanoparticles achieved targeted combination therapy through a sustained-release mechanism, resulting in comprehensive retinal protection: attenuating oxidative damage, promoting microglial M2 polarization, and significantly inhibiting RGC apoptosis. Importantly, functional assessments demonstrated substantial recovery of a-wave and b-wave amplitudes in electroretinography (ERG) and enhanced P1-wave amplitudes in flash visual evoked potential (FVEP) recordings. Mechanistically, proteomic analysis revealed suppression of Nogo-A expression, which modulated NF-κB signaling and the intrinsic apoptotic pathway, involving caspase-8 inhibition and BCL-2/BAX balance restoration. These actions preserved retinal structural integrity and restored visual function, as confirmed by electroretinography, with excellent biosafety profiles, offering a promising multi-target therapeutic strategy for neurodegenerative retinal diseases.
    Keywords:  MOF; Oxidative stress; Polydopamine; Retinal ganglion cells; Retinal ischemia reperfusion injury
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103239
  13. Front Immunol. 2026 ;17 1831652
    Enhancing cancer vaccine efficacy via electrostatic engineering of an FcγR-targeted protein.
    Chiao-Chieh Wu, Chia-Ling Chen, Chen-Yi Chiang, Ling-Ling Tu, Shih-Jen Liu, Chih-Hsiang Leng, Hisn-Wei Chen.
       Background: Effective cancer vaccines require delivery platforms that can simultaneously enhance immune responses, maintain safety, and simplify the formulation process. This study aimed to develop a novel vaccine delivery system based on the Staphylococcus aureus-derived formyl peptide receptor-like 1 inhibitory protein (FLIPr), which naturally targets Fcγ receptors on antigen-presenting cells.
    Methods: A recombinant variant, rF9R, was engineered by adding nine arginine residues to the C-terminus of FLIPr to facilitate electrostatic binding with anionic components. To optimize this interaction, epitopes were modified with five aspartic acid residues. The platform's ability to form stable complexes with peptides, CpG oligodeoxynucleotides, and protein antigens was evaluated. The efficacy of the rF9R/rE7m complex was subsequently tested in tumor models to assess CD8+ T-cell activation and tumor regression.
    Results: The rF9R protein successfully bound peptides and antigens to form stable complexes, significantly enhancing antigen delivery and immune activation. In vivo results demonstrated that the rF9R/rE7m complex-both as a standalone treatment and when combined with CpG-elicited robust CD8+ T-cell responses. This immune activation led to significant tumor regression in the studied models.
    Conclusion: The rF9R platform functions as both an efficient carrier and a potent immunostimulatory component. By providing a simple and versatile method for delivering peptide and subunit vaccines, rF9R represents a promising strategy for advancing cancer immunotherapy.
    Keywords:  FLIPr; antitumor efficacy; cancer vaccines; immunogenicity; immunotherapy
    DOI:  https://doi.org/10.3389/fimmu.2026.1831652
  14. J Control Release. 2026 Jun 09. pii: S0168-3659(26)00493-1. [Epub ahead of print]396 115090
    Nanoparticle-mediated intracellular delivery of biomolecules to plants: From mechanistic insights to translational challenges.
    Yao Jiang, Ying Sun, Chaobo Huang, Ranhua Xiong.
      Achieving intracellular delivery of biomolecules in plants represents the foundation for next-generation genetic engineering and trait optimization. Conventional transformation techniques face intrinsic limitations including host-specific compatibility issues and subcellular targeting inaccuracy. Nanoparticle-mediated delivery platforms emerge as transformative solutions offering broad applicability across multiple plant species, spatiotemporal control, and organelle-level precision. This review first analyzes the structure-activity relationships governing nanoparticle-plant interactions, with particular focus on nanocarrier dimension optimization, zeta potential modulation, and surface ligand engineering to overcome multi-membrane barriers (cell wall, nuclear envelope, chloroplast double membrane). Further, we critically evaluate cutting-edge functionalization strategies encompassing covalent conjugation and supramolecular assembly that enable the exploitation of biomimetic transport channels. These advances facilitate organelle-specific cargo delivery to chloroplasts, mitochondria, and nuclei, leveraging both physical penetration and biological recognition pathways. In addition, we highlight recent scientific progress and emerging translational efforts. Despite laboratory-scale breakthroughs, translational bottlenecks persist in nanotoxicity mitigation, environmental stability assurance, GMP-compliant scale-up, technical adoption across plant biotechnology platforms, and regulatory framework establishment. The established design principles and emerging technical roadmap presented herein illuminate pathways toward plant bioengineering, a shift addressing pressing agricultural challenges from climate resilience to carbon-negative bioproduction.
    Keywords:  Engineered nanoparticles; Functional modification; Fundamental progress; Intracellular precision delivery; Organelles; Translational challenges
    DOI:  https://doi.org/10.1016/j.jconrel.2026.115090
  15. J Adv Res. 2026 Jun 06. pii: S2090-1232(26)00456-X. [Epub ahead of print]
    Innovative mucosal nanocarrier systems for enhanced immune response against respiratory pathogens.
    Zhenzhen Zhang, Rong Chen, Xiang Zhou, Hui Wang, Hanfei Gong, Changle Wang, Ruoyu Hao, Ting Yuan, Fei Hao, Qiyan Xiong, Bo Tang, Chao Zhang, Zhixin Feng.
       INTRODUCTION: Effective pulmonary vaccination remains limited by the pulmonary surfactant (PS) barrier and inefficient intracellular delivery of vaccine cargo to alveolar antigen-presenting cells, particularly alveolar macrophages. Inspired by the natural compatibility of alveolar macrophage-derived vesicles with the alveolar environment, we developed biomimetic alveolar macrophage membrane vesicles (AMVs) as a mucosal nanocarrier platform.
    OBJECTIVES: This study aimed to develop a nanovaccine platform that addresses key extracellular and intracellular barriers in the lung and to evaluate its immunogenicity and protective efficacy in multiple respiratory pathogen models.
    METHODS: AMVs were engineered to improve performance in the PS environment and to achieve preferential uptake by alveolar macrophages. An Antigen Capture and Cytosolic Delivery System (ACCDS) was incorporated, comprising: (1) an engineered surfactant protein A domain for broad pathogen binding; (2) a pH-responsive listeriolysin O module designed to facilitate endo/lysosomal escape and enhance cytosolic access of cargo; and (3) encapsulated Poly(I:C) to activate TLR3 and support RIG-I/MDA5-associated signaling.
    RESULTS: AMV-ACCDS-Poly(I:C) showed improved delivery performance in the PS-associated environment and preferential uptake by alveolar macrophages compared with synthetic nanoparticles and a commercial transfection reagent. Dual innate activation was associated with stronger IFN-β and IL-18 responses than those induced by the tested control formulations. The platform promoted the local establishment and/or differentiation of lung-resident memory-like CD8+ T cells and was accompanied by IL-18-associated metabolic remodeling. In prime-boost studies, it conferred complete protection in lethal influenza and pseudorabies virus challenge models and reduced pulmonary burden in a Mycoplasma infection model.
    CONCLUSION: AMV-ACCDS-Poly(I:C) provides a biomimetic strategy to address key barriers in pulmonary vaccination and supports the potential of membrane-based mucosal vaccine systems for protection against respiratory pathogens.
    Keywords:  Alveolar macrophages; Antigen capture and cytosolic delivery system; Artificial cell membrane vesicles; Mucosal immunization; Pulmonary surfactant barrier
    DOI:  https://doi.org/10.1016/j.jare.2026.06.002
  16. J Transl Med. 2026 Jun 13.
    Macrophage immunometabolism in stroke: a view from single-cell and nano technologies.
    Yajun Zhu, Zichao Huang, Xiaoguo Li, Jiru Zhou, Xingwei Lei, Fuming Liang, Jin Yan, Hongji Deng, Xiaochuan Sun, Zongduo Guo.
       BACKGROUND: Stroke induces profound neuroinflammation in which macrophages play a complex dual role, contributing to both injury and repair. The traditional M1/M2 classification is increasingly recognized as oversimplified. Advances in single-cell RNA sequencing (scRNA-seq) have revealed a spectrum of dynamic macrophage subpopulations with distinct functional and metabolic states, fundamentally reshaping our understanding of post-stroke immunity.
    MAIN BODY: This review synthesizes recent insights into macrophage heterogeneity from a single-cell perspective, highlighting novel subsets such as an LCP1⁺ population defined by coupled glycolipid metabolism. We discuss how metabolic reprogramming, including glycolysis, oxidative phosphorylation, cholesterol metabolism, hypoxia‑driven gradients, and mitochondrial dynamics, critically underpins macrophage polarization. Glycolysis fuels pro-inflammatory (M1-like) responses, whereas oxidative phosphorylation and fatty acid oxidation support anti-inflammatory and reparative (M2-like) functions. We further explore innovative nano‑therapeutic strategies, including engineered liposomes, exosomes, and responsive polymeric nanoparticles, that enable spatiotemporally precise modulation of macrophage activity. Based on these advances, we propose an integrative framework that directly links scRNA‑seq‑defined macrophage subsets to their metabolic pathways, druggable targets, and tailored nano‑interventions. We also critically examine clinical translation barriers and prioritize actionable targets (e.g., CCR2, PPARγ, Nrf2) for future stroke therapy.
    CONCLUSIONS: The convergence of single‑cell genomics, immunometabolism, and nanotechnology offers a transformative path toward precision immunomodulation in stroke. Moving beyond the static M1/M2 dichotomy to target macrophage subpopulations and their metabolic drivers guided by an integrated framework holds significant promise for developing more effective therapies.
    DOI:  https://doi.org/10.1186/s12967-026-08412-7
  17. Int J Pharm. 2026 Jun 12. pii: S0378-5173(26)00520-X. [Epub ahead of print] 127072
    Isoquercitrin-loaded adipose-derived stem cell exosomes synchronize immunomodulation and neurovascular remodeling to accelerate spinal cord regeneration.
    Wenjun Xia, Shuaiqi Liu, Tian Gao, Fei Xue, Qian Guo, Zhaohui Lou, Youfu He.
      Spinal cord injury (SCI) involves complex and interconnected pathological processes, including microglia-driven inflammation, vascular disruption, and impaired neuronal metabolic homeostasis, which collectively limit functional recovery. Here, we developed an isoquercitrin-loaded adipose-derived stem cell exosomes formulation (IQC@ADSCs-EXOs) as a natural nanocarrier delivery platform to coordinately modulate key cellular components within the lesion niche. IQC@ADSCs-EXOs exhibited typical vesicular morphology with nanoscale size distribution and a negative surface potential, and were efficiently internalized by microglia, endothelial cells (ECs), and neurons. Functionally, IQC@ADSCs-EXOs attenuated myelin debris-induced lipid droplet accumulation, lipid peroxidation, and intracellular ROS in BV2 cells, accompanied by a shift toward an anti-inflammatory phenotype. Meanwhile, IQC@ADSCs-EXOs promoted endothelial proliferation, migration, and tube formation, and enhanced mitochondrial activity with increased neurite outgrowth in PC12 cells. In a mouse contusive SCI model, local administration of IQC@ADSCs-EXOs was associated with improved vascular rebuilding, reduced neuroinflammation, enhanced axonal regeneration, and better locomotor and electrophysiological outcomes compared with controls. Collectively, these findings support IQC@ADSCs-EXOs as a nanotherapeutic platform with multicellular targeting capacity and translational potential for SCI repair.
    Keywords:  Adipose-derived stem cells exosomes; Angiogenesis; Microglia; Mitochondrial metabolism; Spinal cord injury
    DOI:  https://doi.org/10.1016/j.ijpharm.2026.127072
  18. Tissue Cell. 2026 Jun 09. pii: S0040-8166(26)00384-8. [Epub ahead of print]103 103690
    Exosomes from adipose-derived stem cells preconditioned with 650- or 810-nm photobiomodulation enhance cutaneous wound healing in rats.
    Abdollah Amini, Seyed Mahmoud Hashemi, Fatemeh Ahangari, Soroush Bayat, Mobina Tohidian, Richard Albright, Sufan Chien, Mohammad Bayat.
      This study investigated whether photobiomodulation (PBM) preconditioning at 650 nm or 810 nm modifies the regenerative potential of exosomes secreted by human adipose-derived stem cells (HADSCs) during full-thickness acute skin wound healing in rats. Although both wavelengths have been shown to enhance ADSC viability, proliferation, and exosome release in vitro, their in vivo reparative efficacy remains incompletely defined. We had 4 groups: untreated controls, animals treated with exosomes from non-preconditioned HADSCs, and two groups receiving exosomes derived from HADSCs exposed to either 650-nm or 810-nm PBM. Exosomes were administered at a concentration of 150 μg/mL and a total dose of 450 μg per animal. Wound tissues were harvested on day 8 for biomechanical testing, stereological evaluation of tissue components, and analysis of miR-21, VEGF-A, and HIF-1α expression. The EXO 650, and EXO 810 groups demonstrated 119%, and 105% increases in Stress High Load capacity compared to control group (both p < 0.001). The EXO 650 and EXO 810 wavelengths resulted in 58% and 67% increase in fibroblast population (p < 0.01, p < 0.001). EXO 650 and EXO 810 wavelengths showed 43%, and 64% increases in the number of new blood vessels (p < 0.01, p < 0.001) over control values. Molecular signaling analysis via fold-change quantification indicates that Exo 650 and Exo 810 wavelengths achieved 1.65-fold, and 1.55-fold increases in VEGF-A expression relative to the control group (p < 0.001, p < 0.01). For miR-21, the Exo 650 and Exo 810 wavelengths achieved 1.45-fold, and 1.4-fold increases (both p < 0.001). In conclusion, Exosomes from HADSCs preconditioned with 650 or 810 nm PBM accelerated the proliferative phase of wound healing, improving biomechanical strength, fibroblast density, and angiogenesis versus controls. These effects were associated with reduced inflammation and upregulation of the miR-21/VEGF-A/HIF-1α axis. No significant differences were observed between the two wavelengths.
    Keywords:  Cutaneous wound healing; Exosomes; Photobiomodulation therapy; Rat; Stem cell preconditioning
    DOI:  https://doi.org/10.1016/j.tice.2026.103690
  19. World J Microbiol Biotechnol. 2026 Jun 08. pii: 337. [Epub ahead of print]42(7):
    Engineering peroxisomal cofactor systems in Saccharomyces cerevisiae for enhanced biosynthesis of α-humulene.
    Yue Li, Ying Tian, Yuanyuan Ma, Chuanbo Zhang, Wenyu Lu.
      With the rapid development of synthetic biology and metabolic engineering, compartmentalized biosynthesis of natural products has attracted extensive attention, in which peroxisomes present unique advantages over other subcellular organelles. Herein, the peroxisomes cofactor balance was systematically engineered in Saccharomyces cerevisiae BY4741 to achieve efficient biosynthesis of α‑humulene. Firstly, the cytoplasmic mevalonate (MVA) pathway and AcHS2 were targeted to peroxisomes using the ScPEX5*-oPTS1* orthogonal transport system, resulting in strain LM07 with an α-humulene titer of 978.92 mg/L. Subsequently, co-expression of POX1 and FOX2 enhanced peroxisomal acetyl-CoA supply, knockout of MDH3 increased NADH availability, and overexpression of PCD1, Cv1693, PXN, and ANT1 established a peroxisomal CoA metabolic cycle, which increased the titer by 47.97% to 1448.46 mg/L. Furthermore, we conducted a screening of α-humulene synthases from different sources and enhanced the α-humulene titer in yeast by 110.71%. Finally, a cytoplasm-peroxisome dual-compartment engineering strategy was implemented to optimize the cytoplasmic α-humulene synthetic pathway. The engineered strain LM27 produced 2502.69 mg/L α-humulene in shake-flask fermentation. This regulatory strategy provides a valuable technical reference for the efficient biosynthesis of other terpenoids in S. cerevisiae.
    Keywords:   Saccharomyces cerevisiae ; Cofactor engineering; Peroxisome; Sesquiterpene; α-humulene
    DOI:  https://doi.org/10.1007/s11274-026-05060-3
  20. Antioxid Redox Signal. 2026 Jun 08. 15230864261443868
    Targeting the IKKα/NF-κB Axis with SGEC-Derived Exosomal miR-23b-3p Rebalances Treg/Th17 Immunity in Sjögren's Syndrome.
    Yan Cai, Xianzhen Wang, Jing Feng, Changyong E.
       BACKGROUND: Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by chronic inflammation, oxidative stress, and progressive salivary gland dysfunction. Current therapies remain limited in efficacy.
    AIM: This study explored the regulatory effect of exosome (Exo)-transported miR-23b-3p on the IκB kinase alpha (IKKα)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling axis in SS.
    METHODS: Key SS-related microRNAs (miRNAs) were identified by integrating weighted gene co-expression network analysis with machine-learning-based transcriptomic profiling. Target genes and functional pathways were analyzed by bioinformatics methods. The direct binding between miR-23b and IKKα (CHUK) was validated by a dual-luciferase reporter assay. An in vitro SS cell model was established to examine the effects of miR-23b-3p on the IKKα/NF-κB pathway, oxidative stress, inflammation, and apoptosis. miR-23b-3p was loaded into salivary gland epithelial cell-derived Exos (SGEC-Exos) via electroporation. In vitro coculture experiments assessed reactive oxygen species (ROS) levels, inflammatory cytokines, Treg/Th17 balance, and cell apoptosis. In vivo effects were evaluated in NOD/Ltj mice by measuring salivary flow rate, histopathology, and expression of salivary-function-related proteins AQP5 and GPER.
    RESULTS: SGEC-Exos@miR-23b-3p significantly suppressed IKKα expression and NF-κB activation, reduced ROS production, and modulated immune responses by restoring the Treg/Th17 balance. It also inhibited apoptosis by decreasing Bax and caspase-3 expression and increasing Bcl-2 levels. These effects were partially reversed by reactivation of the IKKα/NF-κB pathway. In NOD/Ltj mice, SGEC-Exos@miR-23b-3p improved salivary flow, alleviated glandular pathology, and upregulated AQP5 and GPER expression.
    CONCLUSIONS: SGEC-Exos@miR-23b-3p offers a translational approach to address oxidative stress, immune imbalance, and glandular injury in SS, highlighting the potential of Exo-based miRNA therapy. Antioxid. Redox Signal. 00, 000-000.
    Keywords:  Sjögren’s syndrome; exosomes; miR-23b-3p; salivary gland epithelial cells
    DOI:  https://doi.org/10.1177/15230864261443868
  21. Nat Commun. 2026 Jun 12.
    Engineering human PEG10-based nanoparticles for RNA self-packaging, delivery and cancer therapy.
    Pin-Yan Chen, Ting-Lun Tien, Vy Anh Truong, Quyen Thuc Dang, Nuong Thi Kieu Nguyen, Pin-Hsin Chen, Yu-Chen Hu.
      PEG10 protein was recently uncovered to self-assemble and self-package its own mRNA into nanoparticles, but the particles require expensive transfection for production and have yet to be explored for cancer therapy. Here we develop a human PEG10-based nanoparticles (PBNPs) platform for cargo RNA self-packaging and delivery for cancer therapy. We design a process to improve the PBNPs production for 11.3-fold while reducing the cost. The PBNPs self-package mRNA of at least 7336 nucleotides and remain stable for 7 months. We engineer the PBNPs surface and tremendously improve mRNA delivery efficiencies to various cancer cells, particularly colon cancer cells (≈71%). We further reprogram the PBNPs to deliver an immunotherapeutic mRNA cocktail to colon cancer cells, which elicits T cell responses in vitro. In vivo co-administration of the engineered PBNPs and chemodrug in female mice synergizes immune responses and promotes anti-cancer efficacy, implicating the potential of PBNPs as an RNA delivery vehicle for immunotherapy.
    DOI:  https://doi.org/10.1038/s41467-026-74352-x
  22. Biomed Res Int. 2026 ;2026(1): e6652338
    Exosomes From Adipose-Derived Mesenchymal Stem Cells: A New Prospective Therapy of Diabetic Foot Ulcer.
    Rong Zhang, Zhanshuai Song, Juan Zhang, Wenwen Zhang, Linlin Li, Feifei Mou, Yongtao Su, Kai Mou.
      Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes, characterized by high rates of morbidity, disability, and mortality. Current treatment modalities for DFU primarily include surgical debridement, negative-pressure wound therapy, and anti-infection measures. However, these approaches are limited by prolonged treatment duration, high costs, and suboptimal therapeutic outcomes. Adipose-derived mesenchymal stem cells (ADMSCs) have garnered significant attention in wound repair and tissue regeneration due to their ability to secrete a variety of cytokines involved in the healing process. Exosomes, as key mediators of the paracrine effects underlying the therapeutic benefits of ADMSCs, are emerging as promising agents for wound repair. As a novel therapeutic strategy, exosomes have been increasingly investigated for the treatment of DFU. In this review, we summarize the applications and therapeutic potential of ADMSC-exosomes in DFU, aiming to provide a valuable reference for its clinical management.
    Keywords:  diabetic foot ulcer; exosomes; mesenchymal stem cell-derived exosomes; new therapy
    DOI:  https://doi.org/10.1155/bmri/6652338
  23. Bioact Mater. 2026 Nov;65 28-42
    A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment.
    Wenchao Wang, Wenxiang Huo, Dingfei Qian, Peihong Hou, Cheng Su, Shengyao Sun, Yawei Yao, Jinlong Ma, Linhao Hou, Jiayan Wu, Yongming Chen, Fanqi Hu, Tianyu Zhao, Xuesong Zhang.
      The nucleus pulposus (NP), the core shock-absorbing component of the intervertebral disc (IVD), plays a vital role in the pathogenesis of intervertebral disc degeneration (IVDD). Here, we uncover that degenerative NP tissue under mechanical stress is characterized by upregulated PIEZO1 and accumulation of cell-free DNA (cfDNA). Specific inhibition or knockout of PIEZO1 suppresses the cfDNA-induced NP degeneration. Mechanistically, PIEZO1-mediated calcium overload triggers mitochondrial DNA (mtDNA) leakage, initiating a cascade that culminates in MAFB-dependent activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway. Targeting the PIEZO1-cfDNA-MAFB-NLRP3 axis, we developed a hydrogel nano composite system (HA-F127@MCC950 SiNPs) containing amino-functionalized SiO2 nanoparticles (SiNPs) loaded with pyroptosis antagonist MCC950, embedded within hyaluronic acid (HA) and pluronic F127 (F127). The engineered hydrogel possesses dual effects in cfDNA scavenging and NLRP3 suppression in NP cells (NPCs). Moreover, this approach markedly attenuated NP degeneration progression in rat models of cfDNA-induced and temporary compression model (TCM)-induced IVDD. Collectively, this nucleic acid clearance strategy provides new insights for IVDD treatment.
    Keywords:  Intervertebral disc degeneration; Mechanical stress; NLRP3; PIEZO1; cfDNA
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.05.027
  24. Int J Mol Sci. 2026 Jun 05. pii: 5112. [Epub ahead of print]27(11):
    The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System.
    Arpita Ghosh-Mitra, Mansi Patel, Samarjit Das.
      Mitochondrial dysfunction is not merely a byproduct of transformation but a driver of tumorigenesis, metastasis, and therapeutic resistance. Recent advancements in intercellular communication have identified Extracellular Vesicles (EVs) or exosomes as critical mediators that bridge the gap between the tumor and its microenvironment (TME). These EVs contain a complex repertoire of bioactive cargo, including proteins, lipids, and RNAs. Among the class of RNAs, small non-coding RNAs, microRNAs (miRNAs), are the most abundantly expressed bioactive compounds that are selectively packaged and delivered to recipient cells. EV-delivered miRNAs can target nuclear-encoded mitochondrial genes and have also been reported to localize to mitochondria (mitomiRs), where they function as post-transcriptional regulators of bioenergetic and mitochondrial dynamic adaptations that support tumor progression. This review explores the "EV-miRNA-Mitochondria Axis", delineating the molecular mechanisms by which EV-carried miRNAs reprogram the "Mitochondrial Information Processing System" (MIPS) - a signaling network where mitochondria integrate metabolic cues (e.g., ROS, calcium flux) to dictate critical biological outcomes, such as immune regulation and cell survival. We summarized specific sorting machineries (e.g., hnRNPA2B1, Lupus La) that package oncogenic miRNAs into EVs and how these cargoes hijack mitochondrial function upon delivery. Specifically, we discussed how EV-miRNAs induce metabolic shifts, manipulate mitochondrial dynamics (fission/fusion), and inhibit the intrinsic apoptosis to drive cancer progression. Finally, we highlighted the dual utility of these EV-miRNAs as drivers of pathogenesis and promising non-invasive biomarkers for early diagnosis, prognostic and therapeutic monitoring.
    Keywords:  EV; cancer; exosomes; extracellular vesicles; miRNA; microRNA; mitochondria
    DOI:  https://doi.org/10.3390/ijms27115112
  25. Pathol Res Pract. 2026 Jun 06. pii: S0344-0338(26)00232-3. [Epub ahead of print]286 156579
    Tumor-derived extracellular vesicles: From biogenesis and molecular composition to translational therapeutics.
    Sameer M Sheikh, Ujban Md Hussain, Satish S Meshram, Harekrishna Yadav, Abhaysingh D Deshmukh, Shrushti P Dhakare, Veena Belgamwar, Satyendra K Prasad.
      Extracellular vesicles (EVs) have emerged as vital mediators of cell-to-cell communication in cancer. Tumor-derived EVs (TD-EVs) actively remodel the tumor microenvironment (TME) by transferring a complex cargo of oncogenic proteins, regulatory RNAs, lipids, and metabolites, thereby influencing tumor growth, angiogenesis, metastasis, and immune modulation. This review explains the biogenesis pathways and molecular composition of TD-EVs, highlighting how endosomal sorting complexes, Rab GTPases, tetraspanins, and lipid metabolism collectively determine vesicle release and functional specificity. Comparative analyses of proteomic, transcriptomic, and lipidomic profiles reveal that TD-EVs carry tumor-specific signatures that can serve as non-invasive diagnostic and prognostic biomarkers. Mechanistic insights emphasize the crosstalk between tumor and stromal cells mediated by EVs, which reprogram fibroblasts, immune cells, and endothelial cells toward pro-tumorigenic phenotypes. Advances in EV engineering, encompassing surface modification, cargo loading, and hybrid synthetic vesicle design, have expanded their role as nanocarriers for targeted drug and gene delivery. In addition, EV imaging and tracking innovations such as fluorescence labeling, magnetic resonance-based probes, and bioluminescent reporters enable real-time in vivo visualization and biodistribution analysis. This review critically evaluates emerging preclinical models and early-phase clinical applications of EV-based nanotherapeutics, while explicitly addressing the rigorous translational bottlenecks, such as Good Manufacturing Practice (GMP) scalability, pharmacokinetic unpredictability, and inherent biological heterogeneity, that currently impede their progression into routine clinical use. The findings position TD-EVs as both critical regulators of tumor biology and versatile platforms for precision cancer therapy, bridging molecular oncology with next-generation nanomedicine.
    Keywords:  Drug Delivery Systems; Exosome Engineering; Extracellular Vesicles (EVs); Nanomedicine; Precision Medicine; Targeted Therapy
    DOI:  https://doi.org/10.1016/j.prp.2026.156579
  26. J Agric Food Chem. 2026 Jun 08.
    Identification, Characterization, and Engineering of a Novel 3-Ketosteroid-Δ1-Dehydrogenase.
    Ying Zhang, Ziyi Zhou, Hanlu Zou, Yan Wang, Yuanyuan Chen, Huimin Liu, Xinxin Xu, Mengfei Long, Guojian Liao.
      C1,2-dehydrogenation of sterols by Δ1-KstD is critical for synthesizing bioactive steroidal intermediates (e.g., ADD) from agricultural phytosterol byproducts. However, fungal Δ1-KstD enzymes remain underexplored. Here, we identified and characterized a novel Fs_KstD via microbial screening, transcriptomics, and heterologous expression in Escherichia coli. Fs_KstD efficiently catalyzed C1,2-dehydrogenation of 4AD, TS, and PG. Using the iCASE computational model, we engineered the T206L mutant, exhibiting a 142.36% activity increase toward 4AD. Molecular dynamics revealed that T206L optimizes active site conformation and strengthens enzyme-substrate interactions. Under optimized conditions with Tween 80, T206L achieved a 95.22% conversion rate. These findings establish fungal Fs_KstD as a promising biocatalyst for valorizing phytosterol feedstocks into high-value steroid intermediates for agricultural and food chemistry.
    Keywords:  3-ketosteroid-Δ1-dehydrogenase; fungi; rational design
    DOI:  https://doi.org/10.1021/acs.jafc.6c03518
  27. Biotechnol J. 2026 Jun;21(6): e70257
    The Role of Exosomes in Bone Metastasis and Bone Tissue Engineering: Molecular Mechanisms and Therapeutic Opportunities.
    Asrin Emami, Iman Menbari Oskouie.
      Exosomes, nanoscale extracellular vesicles secreted by almost all cell types, have emerged as pivotal mediators of intercellular communication within both pathological and regenerative microenvironments. In bone metastasis, tumor-derived exosomes (TDEs) play a crucial role in the establishment of pre-metastatic niches, modulation of osteoclast-osteoblast balance, and promotion of tumor cell colonization through the transfer of bioactive molecules such as proteins, lipids, and non-coding RNAs. Conversely, in bone tissue engineering, stem cell-derived exosomes have demonstrated remarkable potential to promote osteogenesis, angiogenesis, and tissue regeneration by activating signaling pathways that regulate bone remodeling. This dual role of exosomes-as drivers of disease progression and as therapeutic agents-highlights their significance as both diagnostic biomarkers and next-generation biologics. This review provides a comprehensive overview of the molecular mechanisms underlying exosome-mediated communication in bone metastasis and bone regeneration, summarizes recent advances in exosome-engineered biomaterials, and discusses the translational challenges that must be addressed to enable clinical applications. Understanding the multifaceted functions of exosomes will pave the way for the development of novel exosome-based strategies for the diagnosis and treatment of bone-related diseases.
    Keywords:  bone metastasis; bone tissue engineering; exosomes; regenerative medicine
    DOI:  https://doi.org/10.1002/biot.70257
  28. Acta Biomater. 2026 Jun 06. pii: S1742-7061(26)00376-4. [Epub ahead of print]
    Membrane-Anchoring Naphthalimide-Based Aggregation-Induced Emission Photosensitizers for NIR Fluorescence Imaging and Photodynamic Elimination of Multidrug-Resistant Bacteria.
    Sayed Mir Sayed, Zeeshan Tahir, Yavuz Nuri Ertas.
      Multidrug-resistant (MDR) bacterial infections demand antibacterial strategies that circumvent conventional resistance pathways and enable localized action with minimal host toxicity. Photodynamic therapy (PDT) represents a non-invasive approach; however, its effectiveness is constrained by insufficient bacterial targeting, aggregation-caused quenching, and limited reactive oxygen species (ROS) generation under physiological conditions. Herein, we develop two membrane-anchoring naphthalimide-based aggregation-induced emission (AIE) photosensitizers, TPAPV-NIM-mPy-M and TPAPV-NIM-Py-M, engineered via a donor-π-acceptor molecular design to integrate near-infrared (NIR) fluorescence imaging and antibacterial PDT. Both photosensitizers display visible-light absorption, pronounced AIE characteristics, and NIR emission, providing bright signals upon aggregation and facilitating rapid bacterial visualization. Under low-intensity white-light irradiation, they efficiently generate ROS via both type I and type II pathways, supporting oxygen-dependent and partially oxygen-tolerant mechanisms. The introduction of cationic pyridinium units promotes rapid bacterial binding and membrane-specific localization in Gram-positive and Gram-negative bacteria, thereby confining ROS at the bacterial envelope and enhancing photoinactivation. Notably, TPAPV-NIM-Py-M, benefiting from extended π-conjugation and stronger intramolecular charge transfer, exhibits higher ROS output and superior antibacterial efficacy against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), vancomycin-resistant Enterococcus faecium (VR E. faecium), and multidrug-resistant Escherichia coli (MDR E. coli), while maintaining negligible dark toxicity. Cytotoxicity and hemolysis assays confirm a favorable biocompatibility profile. TPAPV-NIM-Py-M also shows strong antibiofilm activity. Furthermore, TPAPV-NIM-Py-M enables effective in vivo photodynamic elimination of bacteria in an E. coli-infected wound model, significantly accelerating wound closure and tissue regeneration without systemic toxicity. This work establishes a membrane-targeted molecular engineering strategy for high-performance AIE photosensitizers and highlights their potential for image-guided photodynamic treatment of MDR bacterial infections and infected wounds. STATEMENT OF SIGNIFICANCE: Antibiotic resistance and biofilm-associated infections are driving demand for non-antibiotic antibacterial therapies. This study introduces naphthalimide-based aggregation-induced emission photosensitizers that anchor to bacterial membranes, enabling near-infrared fluorescence imaging and localized generation of reactive oxygen species for photodynamic killing. Membrane targeting improves efficacy against both Gram-positive and Gram-negative pathogens, including multidrug-resistant strains, and supports treatment of infected wounds in vivo with good biocompatibility. The work provides a general molecular design strategy for image-guided antimicrobial photodynamic therapy.
    Keywords:  aggregation-induced emission; antibacterial photodynamic therapy; membrane targeting; multidrug-resistant bacteria; wound healing
    DOI:  https://doi.org/10.1016/j.actbio.2026.06.014
  29. Carbohydr Polym. 2026 Sep 01. pii: S0144-8617(26)00589-8. [Epub ahead of print]387 125472
    Polyethylene glycol-maleimide amphiphilic carboxymethyl-hexanoyl chitosan enables cadherin-11-targeted hyaluronan synthase 2 delivery and hyaluronan biosynthesis in osteoarthritis.
    Yong-Ji Chen, Jen-Hao Tsai, Jhe-Lun Hu, Chi-Hsiang Wu, Shan-Wei Yang, San-Yuan Chen, Shwu-Jen Chang.
      Osteoarthritis (OA) is a multifactorial joint disease characterized by progressive cartilage degeneration and chronic inflammation of the synovial membrane. A critical hallmark of OA is the depletion of high-molecular-weight hyaluronan (HA), which impairs lubrication and perpetuates a catabolic microenvironment. To restore endogenous HA biosynthesis, we engineered a cadherin-11 (CDH11)-targeted, pH-responsive nanocarrier (CMN-CDH11) based on amphiphilic carboxymethyl-hexanoyl chitosan-poly(ethylene glycol)-maleimide for the intracellular delivery of hyaluronan synthase 2 (HAS2). These nanocarriers (∼350 nm) leveraged a pH-triggered charge-reversal mechanism, transitioning from -10.88 mV at pH 7.0 to a positive potential of +34.40 mV at pH 4.5. Confocal imaging confirmed that this strategy facilitated endosomal escape, enabling cytosolic delivery of enzymatically active HAS2 for subsequent HA biosynthesis. In vitro results in fibroblast-like synoviocytes demonstrated that CDH11-mediated targeting enhanced cellular association by 2.5-fold, leading to a significant upregulation of HAS2 expression and secretion of bioactive HA with a weight-average molecular weight of 2.05 MDa. In a rabbit ACLT model with three animals per group, HAS2@CMN-CDH11 treatment promoted superior matrix regeneration and sulfated glycosaminoglycan deposition compared with conventional HA injections. We further demonstrated that the HAS2@CMN-CDH11 platform transitioned OA therapy from exogenous HA supplementation to cell-mediated HA production within a 6-week observation period, highlighting its potential as a therapeutic strategy for osteoarthritis.
    Keywords:  Cadherin-11 targeting; Chitosan nanocarriers; Endogenous hyaluronan synthesis; Hyaluronan synthase 2; Osteoarthritis therapy; pH-responsive charge reversal
    DOI:  https://doi.org/10.1016/j.carbpol.2026.125472
  30. Biomaterials. 2026 Jun 05. pii: S0142-9612(26)00376-5. [Epub ahead of print]335 124352
    Orbital hybridization-mediated nanozymes reverse cellular senescence for aged bone regeneration.
    Yuchen Wang, Jikang Cao, Xindi Wang, Tao Liu, Huijun Jiang, Jiandong Jiang, Yuli Wang, Hua Yuan, Shuilin Wu, Fan Wu.
      The regeneration of aged bone is severely compromised by a deteriorating microenvironment characterized by excessive reactive oxygen species (ROS) and consequential endoplasmic reticulum stress (ERS). Herein, we report a biomimetic nanozyme engineered through synergistic p-d orbital hybridization and youthful membrane camouflage to precisely reverse this degenerative cascade. The designed Cu-Sn dual-atom core exhibits exceptional multi-enzymatic activity, scavenging superoxide anions with a 2.5-fold higher efficiency than Cu single-atom control. Mechanistic studies confirm that p-d hybridization redistributes electron density at the Sn site, lowering the energy barrier for ROS adsorption and conversion. This catalytic core is cloaked with a hybrid membrane derived from young mesenchymal stem and endothelial cells, which facilitates targeted delivery to senescent bone niches and provides intrinsic pro-regenerative signals. The composite nanozyme effectively mitigates intracellular oxidative stress and ERS in aged cells, rescuing their osteogenic and angiogenic potential. In an aged mouse model of jawbone defect, a single treatment regimen promoted robust bone regeneration, increasing the bone volume fraction (BV/TV) by 1.7-fold and significantly enhancing new bone mineralization. This work establishes a dual-principle design-orbital hybridization for catalytic amplification and youthful membrane for targeted rejuvenation-offering a versatile platform for treating a spectrum of senescence-associated diseases.
    Keywords:  Aged bone regeneration; Cell membrane biomimetics; Dual-atom nanozymes; Endoplasmic reticulum stress; p-d orbital hybridization
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124352
  31. RSC Chem Biol. 2026 May 25.
    Peptides as programmable molecular scaffolds: from chemical synthesis and engineering to translational medicine.
    Shaoren Yuan, Baljit Kaur, Natalie S Fuchs, Sungwoo Cho, Ashraf N Abdo, Moustafa T Gabr.
      Peptides have evolved from naturally occurring ligands and classical hormones into a versatile and engineerable class of functional molecules. This review provides a comprehensive overview of the technological advances that collectively enable programmable peptide engineering across the entire discovery-to-development pipeline. We first discuss innovations in automated flow synthesis, chemoselective ligation, noncanonical residue incorporation, backbone editing, conformational constraint, and late-stage functionalization that have transformed peptide chemistry from linear sequence assembly into a modular engineering scaffold. We then examine modern discovery approaches, including phage display and mRNA display with the RaPID system, along with computational and AI-enabled design strategies that accelerate hit identification and multi-parameter optimization. Biophysical characterization techniques, cellular target engagement assays, and emerging delivery strategies are also reviewed as critical tools for bridging biochemical potency with intracellular activity. Finally, we discuss the translational barriers facing peptide therapeutics and the engineering strategies that have enabled successful clinical applications. Together, these advances establish a new era in which peptides are no longer viewed as inherently labile biomolecules but as chemically programmable scaffolds whose structures and functions can be precisely engineered.
    DOI:  https://doi.org/10.1039/d6cb00117c
  32. JCI Insight. 2026 Jun 08. pii: e197924. [Epub ahead of print]11(11):
    Serum starvation drives ALIX-dependent extracellular vesicle biogenesis and determines tumor progression.
    Xueqiang Peng, Jiaxing Liu, Guolong Zeng, Yafei Xiao, Zhixiong Hao, Guangpeng He, Hongyuan Jin, Yu Gao, Shilei Tang, Shibo Wei, Yan Li, Yifan Yu, Liang Yang, Hangyu Li.
      Tumor cells are constantly confronted with nutrient deprivation; however, the effect of serum starvation on the remodeling of endosomal compartments and extracellular vesicles (EVs) in tumor cells remains unclear. Here, we found that serum starvation pronouncedly promotes multivesicular body (MVB) biogenesis, EV formation, and cargo selection. Specifically, by generating a constitutively active Rab5Q79L mutant to induce the enlargement of MVB, we revealed for the first time to our knowledge that ANXA3 is sorted into intraluminal vesicles (ILVs) of MVB. Mechanistically, we confirmed that serum starvation regulates the endosomal sorting complex required for transport-associated (ESCRT-associated) protein ALG-2 interacting protein X (ALIX), which recruits ESCRT-III to MVB and binds to annexin A3 (ANXA3) to mediate its sorting into ILVs of MVB. Our study highlights that serum starvation promotes an ALIX-dependent ESCRT-III recruitment pathway, which loads protumor ANXA3 cargo to exert a profound effect on tumor progression.
    Keywords:  Cancer; Cell biology; Oncology
    DOI:  https://doi.org/10.1172/jci.insight.197924
  33. Microsyst Nanoeng. 2026 Jun 08. pii: 224. [Epub ahead of print]12(1):
    Magnetically guided biohybrid microrobots with multimodal locomotion for barrier penetration and multifunctional tumor treatment.
    Yizhi Gong, Mengqi Fan, Zhuluni Fang, Immihan Ceren Yasa.
      Penetrating biological and physical barriers within the body is essential for microrobots to access target sites and achieve effective therapeutic outcomes. However, synthetic microrobots exhibit limited deformability and dynamicity, which are required to navigate tight and complex microenvironments. Here, by leveraging the soft, deformable body of Euglena gracilis, we develop a novel biohybrid microrobot platform that integrates magnetic architectures for controlled propulsion, deformation, and multi-modal locomotion. This design not only preserves the natural motility of microalgae but also leverages their intrinsic therapeutic properties, including chlorophyll-dependent photodynamic therapy (PDT) and immune modulation through E. gracilis natural products. Our biohybrid microrobots navigate through dense three-dimensional biological matrices and around tumor spheroids, exhibiting targeted delivery to tumor regions under both magnetic control and autonomous tumor tropic behavior. This multi-functional platform combines adaptive locomotion, controllable and chemotactic guidance, offering a new paradigm for precision medicine without the need for exogenous drug loading, and has the potential to become a versatile future solution for tumor targeting and dynamic, adaptive treatment in complex medical environments.
    DOI:  https://doi.org/10.1038/s41378-026-01303-3
  34. Bioresour Technol. 2026 Jun 08. pii: S0960-8524(26)01195-8. [Epub ahead of print]458 135113
    CEN-Display: Construction and optimization of a surface display system in Saccharomyces cerevisiae CEN.PK2-1C.
    Zhengzheng Li, Bei Zhang, Meizi Liu, Chenxi Deng, Xinyu Wu, Lixian Wang, Kevin J Verstrepen, Guoping Zhao, Yanfei Zhang.
      Over the past decades, yeast surface display (YSD) technology has emerged as a powerful biotechnological tool with broad applications in biomedicine, industrial catalysis, and environmental science. However, its efficiency, stability and applicability are often limited by proteolytic degradation during secretion in commonly used strains and steric hindrance associated with anchoring architectures. In this study, we developed a high-performance platform, "CEN-Display," using a systematic engineering strategy on the Saccharomyces cerevisiae CEN.PK2-1C strain to expand the YSD toolbox for new chassis. The host chassis was engineered by deleting key vacuolar proteases PEP4/PRB1 to suppress degradation and CAN1 to modulate membrane permeability. And the redesigned display vector incorporated a de novo designed rigid linker (>600 aa) to minimize steric hindrance. Moreover, we conducted a systematic evaluation of eight candidate GPI-anchored proteins and refined cultivation process, specifically optimizing initial inoculation density and induction timing. Eventually, we identified 28_YI as a highly efficient and stable anchor, achieving a sixfold increase in α-galactosidase display efficiency and a 63.5% enhancement in enzymatic activity relative to the conventional Aga1-Aga2 system. Furthermore, the CEN-Display platform exhibited robust compatibility and stability for displaying both the complex enzyme (β-glucosidase, BGL1) and the degradation-prone nanobody (VHH 7D12). Collectively, this work establishes a high-performance yeast surface display platform based on the CEN.PK chassis and provides a foundation for the construction and application of high-performance display systems with broad utility in protein engineering and functional screening.
    Keywords:  28_YI; CEN.PK2-1C; GPI-anchored protein; Glycosylphosphatidylinositol (GPI); Yeast surface display
    DOI:  https://doi.org/10.1016/j.biortech.2026.135113
  35. Mater Today Bio. 2026 Jun;38 103248
    Enhanced ocular delivery of tacrolimus via cationic nanoliposomes: Mitigating inflammation and rebalancing Th17/Treg responses in dry eye disease.
    Lirui Liu, Dan Chen, Siting Sheng, Xueqi Lin, Huiling Zhao, Chujun Liu, Xiang Chen, Yang Ye, Wen Xu.
      Dry eye disease (DED) is a common ocular surface disorder characterized by persistent inflammation and immune imbalance, leading to visual impairment and substantial deterioration in quality of life. Although topical medications remain the mainstay of DED management, their therapeutic effectiveness is frequently limited by poor corneal penetration, low ocular bioavailability, and potential safety issues associated with long-term administration. To address this, we engineered a low-dose cationic tacrolimus nanoliposome delivery system (FK506 NLPs) designed to enhance ocular surface drug availability while targeting immune-inflammatory dysregulation. The positively charged NLPs exhibited prolonged corneal residence via mucoadhesion and improved drug permeation. In a murine model of DED, FK506 NLPs accelerated ocular surface repair, improved tear film stability, and preserved conjunctival goblet cells and lacrimal gland structure. Mechanistically, they suppressed the expression of key proinflammatory mediators in both corneal and lacrimal tissues and restored immune homeostasis by re-establishing the balance between Th17 and regulatory T cells. Importantly, FK506 NLPs also exhibited favorable in vivo biocompatibility. Taken together, these findings demonstrated that FK506 NLPs combined improved ocular delivery with coordinated anti-inflammatory and immunoregulatory effects, highlighting their potential as a promising therapeutic strategy for the management of DED.
    Keywords:  Dry eye; Liposomes; Nanoparticles; Tacrolimus; Th17/Treg
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103248
  36. Discov Nano. 2026 Jun 08. pii: 250. [Epub ahead of print]21(1):
    Emerging paradigms in nanostructured targeted drug delivery systems.
    Anjum N Hasnain, Darshan R Telange.
      Nanostructured drug delivery systems have emerged as powerful and versatile approaches to overcome the limitations of conventional therapeutic strategies, including poor bioavailability, non-specific distribution, and dose-limiting toxicity. By enabling precise control over particle size, surface characteristics, drug loading, and release kinetics, nanocarriers offer enhanced pharmacokinetic and pharmacodynamic performance, along with improved therapeutic specificity. This comprehensive review critically examines emerging paradigms in Nanostructured drug delivery systems, with a particular focus on design strategies, surface functionalization, and translational potential for targeted therapeutics. The review systematically discusses the fundamental principles governing nanocarrier behavior, including physicochemical characteristics, nano-bio interactions, and pharmacokinetic considerations. Various classes of Nanostructured drug delivery systems-such as lipid-based, polymeric, inorganic, carbon-based, and biomimetic carriers-are evaluated with respect to their design rationale, advantages, and limitations. Advanced targeting strategies, including passive and active targeting, ligand-based functionalization, and stealth modifications, are highlighted for their role in enhancing site-specific delivery and therapeutic efficacy. Furthermore, the review explores cellular uptake mechanisms, intracellular trafficking, and subcellular targeting, providing insights into how nanocarriers can be engineered to overcome biological barriers. The translational landscape of nanomedicine is critically assessed, addressing preclinical evaluation, clinical development, manufacturing scalability, regulatory challenges, and safety considerations. Emerging trends, such as artificial intelligence-assisted nanocarrier design, stimuli-responsive systems, bioinspired platforms, and personalized nanomedicine, are also discussed as future directions. In summary, this review underscores the significant progress and remaining challenges in the field of Nanostructured drug delivery systems and highlights their transformative potential in advancing targeted therapeutics and precision medicine.
    Keywords:  Nanocarriers; Nanostructured drug delivery systems; Nano–bio interactions; Pharmacokinetics and pharmacodynamics; Precision medicine; Surface functionalization; Targeted therapeutics; Translational nanomedicine
    DOI:  https://doi.org/10.1186/s11671-026-04685-5
  37. Bioact Mater. 2026 Nov;65 63-75
    Lyophilized bacteria-infected tumor cells for targeted immunotherapy of lung metastases and associated fibrosis.
    Mo Chen, Yueyang Deng, Tianxu Fang, Tianwen Luo, Guojun Chen.
      Lung metastasis remains a major clinical challenge, often associated with poor prognosis due to its highly immunosuppressive microenvironment and fibrosis-induced complications. Current treatment strategies, including chemotherapy, radiotherapy, and immunotherapy, have shown limited efficacy in addressing lung metastases, and less attention has been given to their associated fibrosis. Here, we develop a 'cell-in-cell' delivery platform (i.e., lyophilized bacteria-infected tumor cells (LyoBT)) to simultaneously target lung metastasis and their associated fibrosis. This approach leverages the intrinsic lung tropism of tumor cells and the immunostimulatory properties of both tumor cells and bacteria, while mitigating tumorigenic and pathogenic risks through lyophilization. Notably, bacterial infection led to phenotypic changes in tumor cells. Specifically, characterization of LyoBT revealed upregulated expression of CD47, CD44, and E-cadherin, further enhancing lung targeting. Furthermore, increased calreticulin (CRT) exposure in LyoBT coupled with bacterial immune-stimulatory properties, promoted anti-tumor immunity. In a melanoma lung metastasis model, LyoBT demonstrated efficient accumulation in the lungs, leading to robust anti-tumor immune activation and significant inhibition of tumor progression. Notably, LyoBT also reduced fibrosis-associated immune cell infiltration and cytokine release, alleviating lung metastasis-induced fibrosis. Furthermore, LyoBT served as a drug delivery platform for immune checkpoint inhibitors (aPD-L1), with LyoBT@aPD-L1 demonstrating enhanced therapeutic efficacy. Our findings highlight the potential of LyoBT as a dual-functional strategy to combat both lung metastases and their associated fibrosis, offering a promising new avenue for bacterial-based cancer immunotherapy.
    Keywords:  Bacteria-based immunotherapy; Drug delivery; Fibrosis; Lung metastasis; Lyophilized cell
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.05.044
  38. J Agric Food Chem. 2026 Jun 11.
    Engineered Lactococcus lactis for Oral Delivery of an Antimicrobial Peptide against Enterotoxigenic Escherichia coli in Weaned Piglets.
    Mingyang Hu, Yuwen Li, Lu Zhao, Sina Cha, Yutong Xue, Yueyang Han, Chenyu Xue, Na Dong.
      Food-grade strategies against foodborne pathogens while preserving intestinal health are gaining attention. Here, we developed a regulated delivery platform using Lactococcus lactis engineered to secrete a tandem dimeric antimicrobial peptide (SD). The engineered strain (SDLactis) exhibited stable growth, genetic stability, and tolerance to simulated gastrointestinal conditions. Chloride-responsive SD secretion enabled effective antibacterial activity against enterotoxigenic Escherichia coli (ETEC) K88 in vitro. In ETEC-challenged piglets, oral SDLactis alleviated diarrhea, improved growth, and reduced intestinal injury and inflammation. It strengthened intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Claudin-1,Occludin) and downregulating CFTR. Microbiome analysis revealed that SDLactis partially restored gut microbial diversity, reducing Escherichia-Shigella while enriching Lactobacillus and short-chain fatty acid-producing genera. Overall, food-grade engineered lactic acid bacteria serve as controllable delivery vehicles for antimicrobial peptides, offering a nonantibiotic strategy for pathogen control and gut health management in food and feed applications.
    Keywords:  Escherichia coli; Lactococcus lactis; antimicrobial peptide; food and feed applications; gut health
    DOI:  https://doi.org/10.1021/acs.jafc.5c17784
  39. Blood Adv. 2026 Jun 05. pii: bloodadvances.2025017417. [Epub ahead of print]
    CRISPR application in hematological disorders: from bench to bedside.
    Francesco Ladisa, Eugenio Morelli, Debora Soncini, Matteo Garibotto, Nikhil C Munshi, Mariateresa Fulciniti, Michele Cea.
      Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas genome editing has advanced from an experimental tool to a clinically validated therapeutic platform in hematology. Landmark successes in inherited blood diseases including sickle cell disease, β-thalassemia, and severe combined immunodeficiency, have demonstrated that precise and durable genetic modifications can be safely and effectively implemented in human hematopoietic cells, positioning hematology at the forefront of translational genome editing. Beyond monogenic disease, CRISPR-based approaches are transforming both the biological understanding and treatment of hematologic malignancies by enabling systematic interrogation of cancer dependencies, functional mapping of genetic vulnerabilities, and mechanism-driven target validation, including in vivo and immune-relevant contexts. In parallel, therapeutic applications are emerging through the development of engineered cellular therapies, including edited autologous and allogeneic immune effector cells designed to enhance antitumor efficacy, persistence, and immune evasion. This review synthesizes recent CRISPR-based advances across benign and malignant hematologic diseases. We compare major editing modalities, including nuclease-mediated disruption, base editing, prime editing, and CRISPR-based transcriptional modulation, and highlight key preclinical studies alongside emerging clinical trial data. We also discuss translational challenges that currently limit broader clinical adoption, including delivery and manufacturing scalability, off-target and genotoxicity risks, tumor and immune heterogeneity, and the long-term durability and fitness of edited cell populations. Finally, we outline priorities for the next phase of the field, emphasizing how continued innovation in CRISPR technologies may enable increasingly precise, durable, and mechanism-informed therapeutic strategies in hematology.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017417
  40. Animal Model Exp Med. 2026 Jun 09.
    Cell therapy comparison of dental pulp stem cells, hepatocytes, and their exosomes for liver fibrosis treatment in rats.
    Sahar Rahimi, Seyedeh Mahdieh Khoshnazar, Ali Derakhshani, Nader Shahrokhi.
       BACKGROUND: Excessive extracellular matrix accumulation, primarily as a result of hepatic stellate cell activation, is a hallmark of hepatic fibrosis, a progressive outcome of chronic liver injuries. Recent research studies suggest that stem cells, hepatocytes, and extracellular vesicles may provide therapeutic advantages due to their anti-inflammatory, antioxidative, and regenerative activities. This study aimed to comparatively evaluate the therapeutic efficacy of these agents in a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis.
    METHODS: Liver fibrosis was induced in male Wistar rats via intraperitoneal CCl4 injections for 8 weeks. Then the animals were intravenously administrated stem cells, hepatocytes, hepatocyte-derived exosomes, or stem cell-derived exosomes. Also, a fibrosis, a sham, a intact, and a PBS-treated group were consider the controls. After treatment, protein expression (alpha-smooth muscle actin (α-SMA), desmin), oxidative stress markers (superoxide dismutase, glutathione peroxidase, malondialdehyde), serum biochemical parameters (aspartate aminotransferase, alanine aminotransferase, glucose, uric acid, cholesterol, triglycerides), and fibrosis-related gene expression (matrix metalloproteinase 2 (MMP2), platelete-derived growth factor receptor beta (PDGFRB), transforming growth factor-beta (TGF-β), thymosin beta-10 (TMSB10) and transmembrane protein 176B (TMEM176B)) were assessed.
    RESULTS: Significant liver damage, changed metabolic parameters, increased oxidative stress, and upregulated fibrosis markers were all observed in the fibrosis group. On the contrary, all treatments caused considerable improvements, though exosomes derived from stem cells demonstrated the most significant effects. Along with improved histopathological features, this group exhibited significant decreases in oxidative damage, liver enzymes, and profibrotic marker expression.
    CONCLUSION: Liver fibrosis was considerably reduced by stem cells, hepatocytes, and particularly their exosomes. Exosomes made from stem cells demonstrated the strongest therapeutic effect, confirming their potential as a viable noncellular hepatic fibrosis treatment approach.
    Keywords:  CCl4; dental pulp stem cells; exosomes; hepatocytes; liver fibrosis; stem cells
    DOI:  https://doi.org/10.1002/ame2.70207
  41. Bioact Mater. 2026 Nov;65 128-144
    A closed-loop myocardial infarction theranostic platform activated by macrophage-derived nitric oxide and acidic microenvironment.
    Xuan Xu, Shengnan Li, Yan Chen, Mingxi Li, Runqian Li, Hui Lu, Fang Yang, Jiayi Tong.
      Precise management of the inflammatory response after myocardial infarction necessitates targeted engagement of cellular drivers. Here, we report a pathophysiology-guided theranostic platform that exploits two defining features of pro-inflammatory macrophages, their high-output nitric oxide (NO) production and localized acidic microenvironment, to enable concurrent sensing, quantification, and modulation of post-infarction inflammation. The platform, PM720@NRP, is engineered from platelet membranes encapsulating an NO-responsive NIR-II fluorophore and the immunomodulator FTY720. It delivers three integrated functions: (i) specific, NO-activated NIR-II imaging of inflammatory foci; (ii) machine learning-powered translation of imaging signals into quantitative maps of pro-inflammatory macrophage activity; (iii) acid-triggered release of FTY720 to reprogram macrophages toward a reparative phenotype, synergizing with platelet-derived factors to stimulate angiogenesis. This strategy provided real-time visualization and non-invasive quantification of inflammation, while improving cardiac function and repair. By repurposing pathological biomarkers as intrinsic triggers for diagnosis and treatment, this work establishes a closed-loop, biology-inspired paradigm that autonomously adapts to dynamic disease activity.
    Keywords:  Immunotherapy; Inflammation non-invasive quantification; Machine learning; Myocardial infarction; NO-Responsive nanoprobe
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.05.045
  42. Biofabrication. 2026 Jun 09.
    CAR-T Cell-Derived Exosomes and Cancer Immunotherapy: Advancing Production and Delivery Through Biofabrication.
    Mahmood Razzaghi, Mohammad Hossein Karimi, Jamshid Hadjati, Colin Collins, Mohsen Akbari.
      Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of hematologic malignancies, but it still faces some major barriers in solid tumors because of poor infiltration, the immunosuppressive microenvironment, and sometimes severe toxicities. The CAR-T cellderived exosomes (CAR-T-EXOs) have been emerging as safer and more scalable acellular alternatives that can preserve the tumor-specific CAR recognition and cytotoxic effect or functions, while avoiding the cytokine release syndrome (CRS) and neurotoxicity issues. These nanosized vesicles can penetrate the dense tumor stroma and reprogram the immunosuppressive niches more effectively than the cellular therapies. The recent advances in biofabrication are now enabling the high-yield production, functional validation, and more precise delivery of CAR-T-EXOs. The biofabricated models, including the three-dimensional (3D) spheroids, organoids, bioprinted constructs, and tumor-on-chip systems, offer more physiologically relevant platforms for evaluating exosome trafficking and efficacy. Meanwhile, smart delivery systems such as stimuli-responsive hydrogels, nanofiber scaffolds, and hybrid nanovesicles provide spatiotemporal control over the exosome release. Despite all this promise, the clinical translation is still hindered by the variability in isolation methods, characterization procedures, and the regulatory frameworks. This review tries to integrate immunology, bioengineering, and translational perspectives to outline the biological advantages of the CAR-T-EXOs, to survey the latest biofabrication strategies, and to discuss the regulatory challenges. We also highlight some emerging paradigms, like exosome mimetics, nanorobotics, and personalized tumor-on-chip testing, that are likely to speed up the next generation of safer and more effective exosome-based immunotherapies for solid tumors.
    Keywords:  Biofabrication; CAR-T Cell-Derived Exosomes; CAR-T Cell-Derived Exosomes Biofabrication Exosome Delivery Systems Cancer Immunotherapy Cancer Models Solid Tumor Advanced ther; Cancer Immunotherapy; Cancer Models; Exosome Delivery Systems; Solid Tumor Advanced therapy medicinal products
    DOI:  https://doi.org/10.1088/1758-5090/ae7b0b
  43. Cell Rep. 2026 Jun 09. pii: S2211-1247(26)00588-7. [Epub ahead of print]45(6): 117510
    Peptide-MHC-targeted engineered virus-like particles enable selective priming and gene editing of tumor-specific T cells.
    Brian H Shim, Q Henry Zhao, Jack A Queenan, Blake E Smith, Michael E Birnbaum, David R Liu.
      Tumor-infiltrating lymphocyte (TIL) therapies harness tumor-specific T cells endogenous to a patient's repertoire but their efficacy is limited by challenges such as low frequencies of tumor-specific clonotypes and dysfunctional T cell phenotypes. These challenges necessitate technologies to engineer and reprogram endogenous tumor-specific TILs ex vivo. Here, we present a strategy using engineered virus-like particles (eVLPs) pseudotyped with peptide-major histocompatibility complexes (pMHCs) as a programmable, single-effector platform for selective and coordinated priming, expansion, and genome editing of rare antigen-specific CD8+ T cells among their endogenous polyclonal repertoires. We demonstrate that pMHC-pseudotyped eVLPs (pMHC-eVLPs) deliver T cell function-enhancing base editors to arm polyclonal lymphocytes with enhanced anti-tumor cytotoxicity by selectively expanding and engineering the tumor-specific T cell compartment. Our work establishes pMHC-eVLPs as a platform for enhancing TIL therapy with precision gene edits without the risks of bystander T cell engineering associated with polyclonal TIL engineering approaches.
    Keywords:  CP: cancer; TIL therapy; gene editing; genomics; targeted delivery; virus-like particles
    DOI:  https://doi.org/10.1016/j.celrep.2026.117510
  44. J Biomater Sci Polym Ed. 2026 Jun 08. 1-30
    Chitosan-hyaluronic acid engineered polycaprolactone nanoparticles enhance curcumin antiplasmodial activity and preserve blood-brain barrier integrity.
    James Mwajombe, Rami Ahmed, Retsepile E Maphasa, Clarence Rubaka, Nateiya M Yongolo, Mgeni Mohammed, Anneth Tumbo, Okobi Ekpo, Elingarami Sauli, Chontrelle Willemse, David Fisher, Hulda Swai, Admire Dube.
      Cerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection associated with endothelial activation, neuroinflammation, and disruption of the blood-brain barrier (BBB). While curcumin (Cur) possesses antiplasmodial and anti-inflammatory properties, its therapeutic potential is limited by poor aqueous solubility, rapid metabolism, and insufficient brain bioavailability. In this study, we hypothesized that polysaccharide-driven surface engineering could regulate nanoparticles (NPs) interfacial properties to improve BBB compatibility and antiplasmodial efficacy. Cur-loaded polycaprolactone (PCL) NPs were fabricated through a single-emulsion solvent evaporation technique and sequentially coated with chitosan (CS) and hyaluronic acid (HA) to establish defined structure-property relationships. The resulting nanoformulations were characterized for particle size, surface charge, polysaccharide deposition, encapsulation efficiency (EE), and release kinetics. In-vitro biological performance was evaluated through hemocompatibility, brain endothelial cell viability, BBB integrity through transendothelial electrical resistance measurements, and in-vitro antiplasmodial activity against P. falciparum FCR3. Dual polysaccharide coating produced stable NPs with controlled size, enhanced surface charge, sustained Cur release, and significantly improved endothelial compatibility compared with free Cur and non-hyaluronic-acid formulations. Notably, HA coating strengthened BBB integrity and enhanced antiplasmodial potency. These findings demonstrate that CS- HA surface functionalization governs critical structure-property relationships, highlighting the potential of polysaccharide-engineered nanocarriers for adjunctive CM drug delivery.
    Keywords:  Blood–brain barrier; cerebral-malaria; chitosan; hyaluronic acid; polycaprolactone nanoparticles
    DOI:  https://doi.org/10.1080/09205063.2026.2680995
  45. Int Immunopharmacol. 2026 Jun 11. pii: S1567-5769(26)00796-4. [Epub ahead of print]185 116950
    3D-printed PCL/nHA/SA/COL loaded with M2 macrophage-derived exosomes alleviates the senescence of bone marrow mesenchymal stem cells.
    Lu Yin, Honglan Huang, Jianyu Zhu, Pinting Lin.
       BACKGROUND: The communication between bone marrow mesenchymal stem cells (BMSCs) and macrophages in implant microenvironment is crucial for implantation prognosis. This study explores the potential of PCL/nHA/SA/COL loaded with M2 macrophage-derived exosomes (PCL/nHA/SA/COL@EXOs) on the functions of BMSCs.
    METHODS: PCL/nHA/SA/COL structure is generated by 3D printing. M2 macrophage-derived exosomes (EXOs) are analyzed by TEM and NTR. Gene expression is determined by RT-qPCR, Western blot, and immunofluorescence. KDM4B-induced WNT/P53 signaling-controlled transcription was analyzed using ChIP assay. Cellular behaviors of BMSCs were analyzed by CCK-8, EdU, alizarin red staining, ALP staining, and SAβ-gal staining. 3D-printed PCL/nHA/SA/COL@Exo implantation is performed in mice as well as aged rats.
    RESULTS: PCL/nHA/SA/COL@EXOs exerts more remarkable effects on promoting the proliferation and osteogenic differentiation of BMSCs. Furthermore, PCL/nHA/SA/COL@EXOs inhibits the senescence of BMSCs. Mechanistically, PCL/nHA/SA/COL@EXOs upregulates KDM4B, which mediates histone demethylation and drives WNT/P53 signaling-controlled transcription. In vivo assays confirm that PCL/nHA/SA/COL@EXOs inhibits senescence and mediates new bone regeneration.
    CONCLUSION: PCL/nHA/SA/COL@EXOs effectively inhibits BMSC senescence as well as endows with bone integration performance, which holds great potential for future clinical applications.
    Keywords:  BMSCs; Exosomes; Osteogenesis; PCL/nHA/SA/COL; Senescence
    DOI:  https://doi.org/10.1016/j.intimp.2026.116950
  46. Curr Gene Ther. 2026 Jun 01.
    Surface Functionalization of 3D-Printed Porous Ti-6Al-4V Scaffolds with PDA‑mHA-Col I Composite Coating Drives Macrophage Polarization toward the M2 Phenotype and Promotes Immunomodulation: An In Vitro Study.
    Xu Han, Hailong Yuan, Yi Xiao, Zhen Tang, Gang Tian, Jianyong Gao, Qi Cai, Lisong Lin, Xiaogang Xu.
       OBJECTIVE: To devise a bioactive surface functionalization approach for 3D-printed Ti- 6Al-4V scaffolds that influences macrophage polarization towards the pro-reparative M2 phenotype, therefore enhancing immunomodulation and facilitating good implant-soft tissue integration.
    METHODS: Porous Ti-6Al-4V scaffolds were produced by selective laser melting and then covered with a polydopamine-multi-element-doped hydroxyapatite-type I collagen (PDA-mHA-Col I) composite. The scaffolds' physicochemical characteristics were characterized. Murine RAW264.7 macrophages were cocultured with uncoated (T) or coated (TPMC) scaffolds. Cell viability, proliferation, apoptosis, adhesion, and polarization were assessed via CCK-8 tests, EdU staining, flow cytometry, phalloidin staining, ELISA, and qRT-PCR. The NF-κB, PI3K/Akt, and STAT6 signaling pathways were examined using Western blotting and targeted inhibitors.
    RESULTS: The PDA-mHA-Col I coating improved surface hydrophilicity while maintaining mechanical characteristics. XPS verified effective collagen immobilization, exhibiting a surface nitrogen concentration of 13.03%. The coating demonstrated stability after 7 days in PBS, retaining a nitrogen content of 11.74% and negligible titanium exposure. In comparison to the T group, the TPMC scaffold markedly enhanced macrophage adhesion, proliferation, and spreading, while diminishing apoptosis. It prompted M2 polarization, as shown by reduced expression of M1 markers (iNOS, CD86) and pro-inflammatory cytokines (TNF-α, IL-6), with elevated expression of M2 markers (Arg-1, CD206) and anti-inflammatory cytokines (IL-10, TGF-β1). The TPMC scaffold suppressed the phosphorylation of NF-κB p65 while simultaneously activating PI3K/Akt and STAT6 signaling pathways. The inhibition of PI3K or STAT6 somewhat mitigated the increase of M2 markers.
    DISCUSSION: The coating created a pro-healing milieu by inhibiting inflammatory signals and stimulating pro-reparative pathways, thus tackling a significant obstacle in oral and maxillofacial bone repair.
    CONCLUSIONS: The PDA-mHA-Col I composite coating facilitates macrophage M2 polarization by concurrently inhibiting NF-κB and activating PI3K/Akt/STAT6 signaling, presenting a viable immunomodulatory approach for oral and maxillofacial bone restoration.
    Keywords:  Osteoimmunomodulation; Ti-6Al-4V scaffold; bone tissue engineering.; macrophage polarization; surface functionalization
    DOI:  https://doi.org/10.2174/0115665232490888260525103922
  47. ACS Appl Mater Interfaces. 2026 Jun 11.
    Ag-Based Schottky-Engineered MOF Sonosensitizers Delivered via Dissolvable Microneedles for Sonodynamic Biofilm Eradication and Wound Healing.
    Siyu Fan, Sirong Sun, Heng An, Wenhao Dai, Kai Zhang, Zhou Yang, Xiangdan Meng.
      Biofilms with dense, multibacterial communities formed at the infected wound represent a major pathological barrier to effective healing, which are also closely associated with persistent inflammation and therapeutic failure. Conventional strategies, including mechanical debridement and antibiotic therapy, often result in incomplete biofilm removal and accelerated development of antimicrobial resistance. In this work, we propose a synergistic sonodynamic-microneedle (SDT-MN) platform for efficient biofilm eradication and promoted wound healing. A zirconium-based metal-organic framework sonosensitizer (Ag@Zr-BT), in situ decorated with silver nanoparticles, is engineered to enhance charge separation via Schottky junction formation, thereby amplifying the generation of highly toxic reactive oxygen species (ROS) under ultrasound (US) activation. Ag@Zr-BT with optimal properties is integrated into dissolvable hyaluronic acid-based microneedle patches to facilitate direct drug delivery into biofilms. Under US irradiation, this SDT-MN system exhibits potent antibiofilm activity, efficiently destroying preformed Staphylococcus aureus (S. aureus) biofilms and inhibiting their regrowth. In an infected wound mouse model, SDT-MN-mediated delivery significantly enhances the sonosensitizer's penetration into biofilms and infected tissues, yielding improved therapeutic efficacy. This work establishes an antibiotic-independent therapeutic paradigm that integrates engineered MOF sonosensitizers with a microneedle-assisted delivery system, offering a promising strategy for treating biofilm-associated wound infections.
    Keywords:  iofilm elimination; metal−organic frameworks; microneedle; sonodynamic therapy; wound healing
    DOI:  https://doi.org/10.1021/acsami.6c08500
  48. J Agric Food Chem. 2026 Jun 11.
    Hierarchical Design Synergizing Local Dynamics Optimization and Global Rigidification Unlocks the Catalytic Potential of d-Erythrose-4-phosphate Dehydrogenase.
    Chunxiang Pu, Tenghe Wang, Yu Lv, Yuanming Gai, Xinyi Ren, Huina Dong, Linxia Liu, Jinlong Li, Dawei Zhang.
      A key challenge in enzyme engineering is coordinating local catalytic dynamics with global structural integrity. Here, we present a hierarchical strategy integrating local dynamics optimization with global scaffold rigidification, using d-erythrose-4-phosphate dehydrogenase (Epd) as a model. Guided by evolutionary and conformational network analyses, we first engineered local active-site dynamics, yielding a double mutant (G14A/A234S) with 3-fold higher kcat and improved thermostability (ΔTm = 2 °C). Global rigidification further empowered the preoptimized active site, producing a quadruple mutant (G14A/A234S/T31I/V17I) with 11.2-fold increased kcat and an additional +2 °C Tm rise. Molecular dynamics simulations revealed that distal rigidification suppresses nonproductive fluctuations and enriches catalytically competent conformations. This "inner flexibility, outer rigidity" architecture boosted vitamin B6 production by 3.9-fold. Our work establishes a mechanism-guided paradigm for synergistically enhancing both activity and stability, offering a generalizable framework for engineering industrial biocatalysts.
    Keywords:  catalytic activity and stability; enzyme engineering; hierarchical design; synergistic effects; trade-offs
    DOI:  https://doi.org/10.1021/acs.jafc.6c03307
  49. Front Bioeng Biotechnol. 2026 ;14 1844904
    Immunoengineering in the field of tendon and bone regeneration: immunomodulatory biomaterials, delivery platforms, and preclinical models for chronic diseases.
    Wanxue Wang, Pengfei Yan, Junmiao Liu, Dexi Cui, Qinge Guo, Yu Jiang, Wei Sheng, Yusen Qiao, Xia Zhao.
      The functional and structural reconstruction of the tendon-bone interface (TBI) is a major challenge in orthopedics and sports medicine. Under the influence of chronic degenerative pathologies such as aging, diabetes, and rheumatoid arthritis, the cascading collapse of the local immune-metabolic network disrupts the regenerative microenvironment of the tissue, making the clinical translation of traditional inert physical scaffolds extremely difficult. This review systematically summarizes the latest paradigm shifts in "bone immunoengineering" aimed at overcoming the complex challenges of TBI regeneration. We first decode the core regulatory networks that control interface heterogeneity remodeling, thoroughly analyzing the spatiotemporal polarization dynamics of macrophages, the double-edged effects of the Piezo1-YAP mechanotransduction axis, and the "neuro-immune-skeletal" ternary communication mechanism. Based on this pathological framework, we comprehensively overview next-generation intelligent biophysical and chemical intervention strategies for actively reprogramming extreme microenvironments. These strategies include piezoelectric nanohydrogels for electromechanical-metabolic coupling, Janus asymmetric microfluidic interfaces for multi-ion spatiotemporal rectification, and precise spatial delivery platforms for targeted clearance of senescent cells and engineered exosomes. Furthermore, to overcome the translational barriers between underlying mechanisms and clinical applications, we focus on the cross-scale evolution of preclinical evaluation systems, elaborating on the core value of three-dimensional tendon-bone organoids, microfluidic organ-on-chip systems, and high-resolution spatial transcriptomics. Finally, this review envisions advanced microphysiological systems characterized by closed-loop dynamic adaptive biomaterials, spatiotemporal matching of degradation kinetics, and deep integration with artificial intelligence (AI), highlighting their broad prospects in driving the next-generation of personalized, precise regenerative medicine in orthopedics.
    Keywords:  bone immunology; organoids and organ-on-a-chip; spatial transcriptomics; targeted senescence clearance; tendon-bone interface
    DOI:  https://doi.org/10.3389/fbioe.2026.1844904
  50. Biosens Bioelectron. 2026 Jun 08. pii: S0956-5663(26)00552-X. [Epub ahead of print]311 118920
    Magnetic enrichment and enabled cascade amplification for ultrasensitive SPR analysis of PD-L1+ exosomes.
    Hezhen Liu, Zhaofei Liu, Kwangnak Koh, Hongxia Chen.
      Exosomes serve as stable liquid-biopsy biomarkers for early cancer detection due to their molecular resemblance to parent cells. Here, a magnetic enrichment-assisted surface plasmon resonance (SPR) assay is developed based on Zr/Ce-MOF@Fe3O4 core-satellite nanocomposites for sensitive exosome analysis. The Zr/Ce-MOF is constructed with Zr as the metal node and doped with Ce, exhibiting intrinsic oxidase-like activity through the Ce3+/Ce4+ redox cycle. It catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine without exogenous H2O2, generating a high-refractive-index precipitate that significantly amplifies the SPR signal. The Zr-O-P coordination enables selective capture of phospholipid membranes on exosomes, while Fe3O4 satellites facilitate rapid magnetic enrichment and separation. To further improve specificity and antifouling performance, single-walled carbon nanotube interlayers pre-functionalized with PD-L1 targeting peptides were integrated onto the sensor chip, enabling selective recognition of magnetically enriched PD-L1+ exosomes. The combined refractive-index increase from the nanocomposite and the TMB deposition leads to enhanced SPR responses. Under optimized conditions, the assay achieves a detection limit of 2.16 particles mL-1 (S/N = 3) over a linear range of 102-107 particles mL-1. The total analysis time is within 40 min, and the method shows consistent differentiation between serum samples from cancer patients and healthy donors. This approach provides a practical strategy for the analysis of low abundance exosomal biomarkers.
    Keywords:  Dual-amplification SPR; Exosome PD-L1; Magnetic nanozyme; Process intensification; Zr/Ce-MOF@Fe(3)O(4)
    DOI:  https://doi.org/10.1016/j.bios.2026.118920
  51. Ann Med Surg (Lond). 2026 Jun;88(6): 3872-3873
    Molecular glue degraders versus PROTACs: a novel paradigm in targeted protein degradation.
    Aiman Tahir, Sarum Ali Khan, Eashaal Imtiaz, Muhammad Adnan Qamar.
      Many proteins that cause cancer are still out of reach for regular drugs because they do not have the right structure for small molecules to bind to. Targeted protein degradation (TPD) is a new way to do things. Instead of blocking these proteins, it takes over the cell's own disposal system, the ubiquitin-proteasome system, to get rid of them completely. Two main strategies have emerged: molecular glue degraders, which are small compounds that help an E3 ligase find and tag a target protein, and PROteolysis TArgeting Chimeras (PROTACs), which are engineered bifunctional molecules that physically connect a target to a degradation pathway. Both have shown real promise in early clinical work. PROTACs that target Bruton's tyrosine kinase have shown great response rates in B-cell cancers, and molecular glues that target Ikaros family proteins (IKZF1/3) are still helping people with blood cancers. But there are still problems. PROTACs have trouble dissolving and getting into the body through the mouth. The "hook effect" can make them less effective at higher doses, and both strategies rely heavily on a small number of E3 ligases. To make progress, we need to add more enzymes to our toolkit, design molecules better, and get better data from clinical trials. With cooperation from academia, industry, and regulators, TPD could significantly expand the druggable proteome and transform cancer treatment.
    Keywords:  BTK; E3 ubiquitin ligase; IKZF1/3; PROTACs; cancer therapeutics; hook effect; molecular glue degraders; targeted protein degradation; ubiquitin-proteasome system; undruggable proteome
    DOI:  https://doi.org/10.1097/MS9.0000000000005002
  52. Bioinformation. 2026 ;22(4): 2083-2086
    Estimation of gut microbiome motif associated with active tuberculosis - A case control study.
    Meenal Jain, Tanya Jain, Rajat Nayak, Talha Saad, Akash Wamanrao Karale, Mohammad Ilyas, Ravikant Arjariya.
      Tuberculosis (TB) is the most tenacious health issue affecting individuals globally. Therefore, it is of interest to estimate gut microbiota motifs associated with the outbreak of active TB by incorporating the insights from human case-control data. 106 respondents were categorised into 2 groups: group A with TB and group B controls with 53 respondents in each category. The Shannon diversity index was substantially diminished in affected individuals. The active TB cases exhibited substantially decreased micro-biomes (P < 0.001). Thus, we show the need to develop microbiome-targeted strategies to reduce the incidence of active TB cases and improve their effective management.
    Keywords:  Tuberculosis (TB); dysbiosis; gut microbiota; gut-lung axis
    DOI:  https://doi.org/10.6026/973206300222083
  53. Antonie Van Leeuwenhoek. 2026 Jun 09. pii: 142. [Epub ahead of print]119(7):
    Oral microbiota member Neisseria elongata exosomes-Cassia fistula association targets PTEN/AKT/IL10/IL1β/BAX/BCL-2 signaling pathway in pancreatic cancer immunotherapy.
    Demet Celebi, Ozgur Celebi, Sumeyye Baser, Betul Ari, Bulent Dabanlioglu, Sıdıka Genc, Ali Taghizadehghalehjoughi.
      Pancreatic cancer, characterized by its aggressive progression and limited therapeutic options, remains a malignancy with high mortality rates. This study evaluates the potential of bacterial extracellular vesicles (EVs) as immunotherapeutic carriers, focusing on Neisseria elongata-derived exosomes conjugated with a methanol extract of Cassia fistula, a plant with known anticancer properties. The cytotoxic and apoptotic effects of this complex were systematically analyzed using the PANC-1 pancreatic cancer cell line. MTT and LDH assays revealed a concentration-dependent reduction in cell viability and enhanced cytotoxicity. Mechanistic analyses demonstrated upregulation of pro-apoptotic BAX/BCL-2 ratio and modulation of PTEN/AKT signaling pathways, indicating activation of intrinsic apoptosis. Furthermore, increased levels of the pro-inflammatory cytokine IL-1β and suppression of anti-inflammatory IL-10 suggested immunomodulatory effects. Elevated reactive oxygen species (ROS) levels corroborated the induction of oxidative stress-mediated apoptosis. These results underscore the dual functionality of Neisseria elongata exosomes as both drug carriers and biological response modifiers. The biocompatibility and targeting efficiency of bacterial EVs position them as a novel therapeutic platform for gastrointestinal cancers. This study provides the first preclinical evidence supporting the use of non-pathogenic bacterial exosomes in oncology, highlighting their translational potential for improving treatment outcomes in pancreatic cancer.
    Keywords:  Bacterial exosome; Immunotherapy; Microbiota; Pancreatic cancer
    DOI:  https://doi.org/10.1007/s10482-026-02355-1
  54. Cancers (Basel). 2026 May 22. pii: 1690. [Epub ahead of print]18(11):
    Potential Role of Exosomes in the Pathogenesis, Diagnosis, and Treatment of Ovarian Cancer.
    Anna Markowska, Michał Antoszczak, Janina Markowska, Adam Huczyński.
      Ovarian cancer (OC) remains one of the most lethal gynaecological malignancies, which is mainly due to late diagnosis, high frequency of metastasis, and the risk of developing resistance to systemic therapy. In recent years, exosomes-small extracellular vesicles (EVs) secreted by cancer cells and components of the tumour microenvironment (TME)-have been identified as potential mediators of OC progression. Exosomes participate in intercellular communication and enable the transfer of RNA, proteins, and lipids. These vesicles may modulate the immune response, promote angiogenesis, remodel the extracellular matrix, and drive epithelial-mesenchymal transitions. Exosomes also appear to play a role in the development of drug resistance via direct transfer of resistance factors or indirect modification of TME. In this review article, we summarise current knowledge on the biological role of exosomes in OC pathogenesis. We also discuss their possible diagnostic, prognostic, and therapeutic relevance. The properties and composition of exosomes make them promising noninvasive liquid biomarkers and convenient carriers for anticancer drugs. However, to fully exploit their potential, further large-scale preclinical and clinical studies are required, which should focus primarily on standardising research methods and assessing the safety and efficacy of exosome-based diagnostic and therapeutic methods.
    Keywords:  cancer pathogenesis; exosomes; in vitro; in vivo; liquid biomarkers; nanodelivery systems; ovarian cancer
    DOI:  https://doi.org/10.3390/cancers18111690
  55. J Virol. 2026 Jun 11. e0053726
    A newly developed eGFP-traceable recombinant rhesus lymphocryptovirus, a tool to study viral infection and replication in vitro and ex vivo, confirms gp350 as key for viral entry.
    Erasmus N Kotey, Preeti Sharma, Esther Rodriguez, Jean Patrick Gonzalez-Dahua, Brenda A Tello, Ivana G Reidel, Gabriela M Escalante, Yuqi Zhao, Xiwei Wu, Rodney P Kincaid, Yan Chen, Rebecca L Skalsky, Lorraine Z Mutsvunguma, Javier Gordon Ogembo.
      Epstein-Barr virus (EBV) is implicated in multiple epithelial and lymphoid malignancies worldwide; however, no licensed prophylactic vaccine exists, partly due to the lack of an adequate preclinical animal model to test candidate vaccines. Rhesus lymphocryptovirus (rhLCV) faithfully recapitulates EBV infection, persistence, and pathogenesis in rhesus macaques, offering an invaluable surrogate model. While recombinant EBV expressing enhanced green fluorescent protein (eGFP) enables swift identification of infected cells in vitro and ex vivo, an analogous tool for rhLCV has been lacking. Here, employing en passant recombination technology, we engineered a recombinant rhLCV expressing eGFP (rhLCV.eGFP) from an rhLCV bacterial artificial chromosome derived from the B-lymphoblastoid rhesus macaque cell line LCL 8664. Whole-genome sequencing confirmed sequence integrity, and functional assays demonstrated infectivity in peripheral blood mononuclear cells (PBMCs) from multiple primate species and EBV-susceptible human cell lines, and transformation competence in rhesus macaque PBMCs. To define the role of gp350/220 (gp350) in viral entry, we generated a glycoprotein gp350-deficient mutant (rhLCV.eGFPΔgp350), verified by Sanger sequencing and immunoblotting with a novel anti-gp350 monoclonal antibody (4A6). This mutant exhibited markedly reduced infectivity in rhLCV.eGFP-susceptible human B and epithelial cell lines, underscoring gp350 as a key determinant of B cell tropism, analogous to EBV gp350. Our successful engineering of rhLCV.eGFP provides a powerful platform for visualizing infection, dissecting viral entry mechanisms and cellular tropism, and advancing rhLCV as a surrogate EBV model for vaccine design, defining correlates of protection, studies of latency and reactivation, and preclinical testing of candidate antivirals and immunotherapies.
    IMPORTANCE: Epstein-Barr virus (EBV) infection is associated with various epithelial and lymphoid diseases. The absence of a suitable animal study model for EBV infection has hindered mechanistic studies of pathogenesis and preclinical testing of vaccines and EBV‑targeted therapies. Rhesus lymphocryptovirus (rhLCV), an EBV homolog, accurately recapitulates EBV infection and pathogenesis in rhesus macaques, offering a promising EBV surrogate model. In this study, we engineered a stable recombinant rhLCV expressing enhanced green fluorescent protein (eGFP), rhLCV.eGFP, for easy identification of infected or transformed cells in vitro and ex vivo. Further illustrating the utility of this platform, we also generated a gp350-deficient mutant rhLCV.eGFP and demonstrated markedly reduced infectivity in otherwise susceptible B and epithelial cells, confirming the EBV gp350-homologous role of rhLCV gp350 in viral entry. Thus, rhLCV.eGFP will serve as an invaluable resource for studying EBV biology and advancing the development of EBV prophylactic and therapeutic strategies using the rhLCV surrogate model.
    Keywords:  Epstein-Barr virus; enhanced green fluorescent protein; gp350; host range; monoclonal antibodies; primates; recombinant technology; rhesus lymphocryptovirus
    DOI:  https://doi.org/10.1128/jvi.00537-26
  56. Bioact Mater. 2026 Nov;65 14-27
    Engineered protein nanoclusters reduce liver fibrosis and hepatocellular carcinoma in mice models.
    Tanya Saxena, Gabriela Guedes, Inês Domingues, Hafsa Yagoubi, Léo Guilbaud, William Van den Bossche, Cristina Pangua, Greetje Vande Velde, Bernard Ucakar, Andrea García-Esnaola, Isabelle Leclercq, Aitziber L Cortajarena, Ana Beloqui.
      Long-term liver injury leads to acute hepatitis and chronic liver diseases, including fibrosis and hepatocellular carcinoma (HCC), which frequently necessitate liver transplantation and are associated with poor median survival. Transforming growth factor-β (TGF-β) signalling pathway is a key driver of fibrogenesis and tumor progression. Therapeutic approaches targeting this pathway-via TGF-β receptor blockade or inhibition of its chaperone protein Hsp90- are under pre-clinical and clinical trials, and despite some promising results none of them has been adopted as a definitive therapy. Engineered protein scaffolds have emerged as an attractive alternative owing to their high engineerability and ease of production. In particular, consensus tetratricopeptide repeat (CTPR) proteins are strong candidates because of their modularity, robustness, design flexibility, and amenability to functionalization. Here, we investigate the protein-nanocluster hybrid formulation comprising C390 and nanocluster-stabilizing domain (C390-AuNC) as a Hsp90 inhibitory platform to assess its potential dual anti-fibrotic and anti-tumor activity in two chemically-induced murine liver disease models: acute liver fibrosis and chronic HCC. In the fibrosis model, C390-AuNC markedly suppress the expression of profibrotic markers and promote degradation of collagen fibers in the liver, indicating effective attenuation of fibrogenesis. In the HCC model, C390-AuNC inhibit Hsp90, leading to reduced expression of oncogenic proteins that drive cancer cell proliferation and metastasis, and consequently diminish tumor burden. Collectively, these findings support C390-AuNC as a promising next-generation biotherapeutic platform with low anticipated immunogenicity and high therapeutic potential.
    Keywords:  Anti-fibrotic therapy; Engineered protein therapeutics; Hepatocellular carcinoma; Liver fibrosis; Protein–nanomaterial hybrids
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.05.038
  57. Small. 2026 Jun 07. e74060
    Multivalent Aptamers: Contemporary Engineering Strategies and Biomedical Applications.
    Chengliang Liu, Zhijun Tang, Yilin Zhu, Xuanrong Sun, Lujuan Xu, Xiangsheng Liu.
      Nucleic acid aptamers represent a distinctive class of molecular recognition elements with high binding affinity, excellent chemical stability, and low immunogenicity, making them powerful tools for diverse biomedical applications. Nevertheless, monovalent aptamers are often constrained by limited binding avidity, suboptimal pharmacokinetics, and insufficient biological activation. To address these challenges, multivalent aptamers engineered by assembling multiple units in a well-defined spatial configuration, have emerged to significantly enhance target engagement. This approach improves affinity, specificity, and functional potency, unlocking novel applications inaccessible to monovalent constructs. This review provides a comprehensive overview of recent advances in multivalent aptamer engineering. First, we outline advancements in systematic evolution of ligands by exponential enrichment (SELEX) strategies enabling the direct evolution of multivalent aptamers through rational library design and target-guided selection. Subsequently, we discuss various design approaches for constructing multivalent architectures, alongside their advantages and limitations. Finally, we highlight representative applications, including targeted delivery, therapeutic intervention, molecular imaging, and diagnostics, which capitalize on the multivalency effect to achieve superior biological outcomes in next-generation biomedicine.
    Keywords:  DNA nanotechnology; SELEX; multivalency effect; multivalent aptamers; precision therapeutics; targeted drug delivery
    DOI:  https://doi.org/10.1002/smll.74060
  58. JACC Case Rep. 2026 Jun 12. pii: S2666-0849(26)01969-8. [Epub ahead of print] 108810
    Familial Hypercholesterolemia Combined With Sitosterolemia.
    Jia Sun, Xiaofei Han, Yuqiu He, Yefan Jiang.
       BACKGROUND: Hyperlipidemia is a heterogeneous disorder with genetic and acquired causes, and severe forms may cause vascular calcification and stenosis. Familial hypercholesterolemia (FH) and sitosterolemia are distinct inherited lipid diseases, yet their co-occurrence has not been previously reported.
    CASE SUMMARY: A patient with combined FH and sitosterolemia was identified via genetic testing. Single hypolipidemic therapies failed, whereas combined treatment targeting both disorders achieved significant lipid reduction.
    DISCUSSION: This is to our knowledge the first reported case of concurrent FH and sitosterolemia, expanding the spectrum of inherited hyperlipidemia and highlighting the value of targeted therapy for dual lipid metabolic disorders.
    TAKE-HOME MESSAGE: Genetic testing is indispensable for patients with refractory hyperlipidemia to guide precise combined hypolipidemic treatment.
    Keywords:  case report; familial hypercholesterolemia; hyperlipidemia; sitosterolemia
    DOI:  https://doi.org/10.1016/j.jaccas.2026.108810
  59. Adv Healthc Mater. 2026 Jun 12. e71351
    Folate-Targeted Liposomal Delivery of a Ru(II)-Based Photosensitizer for Photodynamic Tumor Therapy via Pyroptosis Induction.
    Can Shao, Kuang Xu, Jie Peng, Manchang Kou, Ke Xu, Xiaoliang Tang, Zhifa Shen, Jiaxi Ru.
      Pyroptosis has emerged as a promising antitumor strategy offering unique advantages in overcoming apoptosis resistance and activating antitumor immunity. However, the development of drugs capable of achieving spatiotemporally controlled pyroptosis remains a challenge. Herein, we engineered a folate-targeted liposomal nanoplatform to deliver a Ru(II) complex photosensitizer (Ru-Thi@Lipo-FA) for pyroptosis-mediated photodynamic therapy. The Ru(II) complex (Ru-Thi), acting as a photosensitizer, can produce singlet oxygen and superoxide anions and facilitate the photocatalytic oxidation of NADH through multiple mechanisms to kill tumor cells under white light irradiation. Additionally, we encapsulated the complex within folic acid-modified liposomes, which markedly boosted cellular uptake efficiency and tumor targeting, leading to improved therapeutic effects. Mechanistic investigations demonstrated that light-triggered reactive oxygen species generation activates the caspase-3/GSDME-mediated pyroptosis pathway. This study demonstrated a rationally designed, targeted nanoplatform that utilizes a multifunctional Ru(II)-based photosensitizer and induces pyroptosis, providing a viable approach to improve the efficacy of tumor photodynamic therapy.
    Keywords:  Ru(II) complex; folate‐targeted; liposomal delivery; photodynamic therapy; pyroptosis
    DOI:  https://doi.org/10.1002/adhm.71351
  60. NPJ Biosens. 2026 ;3(1): 37
    AI-assisted label-free single-particle analysis of milk-derived extracellular vesicles enabled by nanotweezers.
    Ikjun Hong, Abayomi E Opadele, Guodong Zhu, Yuankai Huo, Justus C Ndukaife.
      Milk-derived extracellular vesicles (mEVs) are promising drug carriers because they can survive the digestive tract, be engineered to avoid immune rejection, and deliver therapeutic cargo to the body. Fully realizing this potential requires precise, single-particle measurements of size, composition, and purity, yet current analytical tools are often slow, require chemical labels. Here we present an electrohydrodynamic nanotweezer platform that rapidly traps thousands of mEVs in parallel, enables label-free interferometric scattering imaging, and uses artificial intelligence for automated analysis. The device employs a thin gold film patterned with a 15 µm hole array that generates radially-converging AC-driven fluid flows to hold vesicles in place in parallel within seconds. By briefly releasing them, we track their Brownian motion to calculate their size from diffusion behavior and estimate refractive index from their interferometric contrast signals to assess sample purity and heterogeneity. This fast, non-perturbative workflow combines scalable trapping, real-time label-free imaging, and automated analysis, offering a powerful approach to studying mEVs and accelerate their use as therapeutic delivery vehicles.
    Keywords:  Engineering; Nanoscience and technology; Physics
    DOI:  https://doi.org/10.1038/s44328-026-00104-y
  61. J Biol Eng. 2026 Jun 06.
    Engineering a PD-L1-sensing synthetic receptor for programmable macrophage response.
    Ilaria De Martino, Luigi Russo, Matteo Marchetti, Velia Siciliano.
      Cellular decision-making relies on the integration of multiple extracellular cues into coordinated functional responses. Synthetic biology provides tools to rewire this process by engineering receptors that convert defined inputs into programmable outputs. Here, we describe a synthetic receptor-based architecture that enables monocytic-like cells to sense an immune-regulatory ligand and conditionally activate a phagocytic program. We engineered a synthetic Notch-based receptor (SNIPR) that detects programmed death-ligand 1 (PD-L1), a broadly expressed immune-regulatory ligand. Upon PD-L1 engagement, the circuit triggers programmable outputs, including expression of a fluorescent reporter or CV1-Fc, as model effector that interferes with CD47-mediated inhibition of phagocytosis. We show that circuit activation scales with PD-L1 levels, partially attenuates PD-1/PD-L1 signaling, and that conditional CV1-Fc expression enhances engulfment of SKOV-3 ovarian cancer cells by THP-1-derived macrophages in vitro. Collectively, this work reframes PD-L1 from an end-point therapeutic target to a programmable input signal for synthetic circuit activation and establishes a modular framework for ligand-responsive control of engineered macrophage behaviour.
    DOI:  https://doi.org/10.1186/s13036-026-00708-y
  62. Nat Commun. 2026 Jun 12.
    Closed-loop iron chelate recycling via molecularly imprinted hydrogels suppresses ferroptosis.
    Yubin Yao, Ting Ying, Chenyu Zong, Tao Ding, Qi Li, Zeyu Han, Fei Wang, Wenguo Cui, Mingzhu Zhang.
      Ferroptosis, an iron-dependent form of oxidative cell death, has emerged as a key driver of osteoarthritis, yet therapeutic strategies remain limited by the inability to safely eliminate iron-chelate complexes after treatment. Their local accumulation can lead to secondary iron release, oxidative stress, and sustained tissue damage. This study presents a hydrogel-based system that enables selective recognition and removal of these complexes through engineered molecular "memory" sites. By encoding the structural features of iron-chelate complexes into the hydrogel network, this system captures and clears them after cellular export, thereby preventing their re-entry and uncontrolled degradation. This approach markedly improves the efficiency and specificity of complex removal compared to non-imprinted materials. In cell and animal models, it restores iron balance, suppresses ferroptosis, and protects cartilage integrity. These findings establish a closed-loop strategy for regulating iron homeostasis and highlight a generalizable materials-based framework for treating iron-driven degenerative diseases.
    DOI:  https://doi.org/10.1038/s41467-026-74330-3
  63. Food Res Int. 2026 Sep 01. pii: S0963-9969(26)01216-0. [Epub ahead of print]239 119533
    Colon-targeted alginate/chitosan microspheres for co-delivery of synbiotics and nanozymes ameliorate inflammatory bowel disease.
    Meiqi Zhao, Hao Zhou, Runci Jiang, Yuting Gao, Peng Zhang, Fengmei Wang.
      Inflammatory bowel disease (IBD) is closely associated with gut dysbiosis and immune imbalance. Synbiotics, combining probiotics and prebiotics, represent a promising dietary strategy; however, their therapeutic efficacy is often limited by poor gastrointestinal stability and insufficient colon delivery. In this study, we developed a colon-targeted delivery system based on alginate/chitosan microspheres for the co-delivery of L. acidophilus, prebiotic stachyose, and a redox-active component. The formulated system exhibited excellent stability under simulated gastrointestinal conditions and effectively preserved probiotic viability. In dextran sulfate sodium (DSS)-induced colitis models, oral administration significantly alleviated disease symptoms, including body weight loss, colon shortening, and histological damage. Mechanistically, treatment restored gut microbial diversity and composition, characterized by enrichment of beneficial genera (e.g., Lactobacillus and Akkermansia) and suppression of opportunistic pathogens. Notably, synbiotic delivery markedly enhanced short-chain fatty acid (SCFA) production, including acetate, propionate, and butyrate, accompanied by upregulation of SCFA receptor expression. These changes were associated with improved intestinal redox status and rebalanced immune responses, as evidenced by increased regulatory T cells and reduced pro-inflammatory Th17 cells. Collectively, this study demonstrates that colon-targeted synbiotic delivery effectively remodels the gut microbiota and metabolic microenvironment, offering a promising food-derived strategy for IBD management.
    Keywords:  Butyrate; Inflammatory bowel disease; Microsphere; Synbiotics
    DOI:  https://doi.org/10.1016/j.foodres.2026.119533
  64. J Control Release. 2026 Jun 09. pii: S0168-3659(26)00486-4. [Epub ahead of print]396 115083
    Engineering nanoplatforms for autoimmune treatment: From synthetic strategies to bioinspired designs.
    Yihan Wang, Celine Ninsuvannakul, Gloria Zhang, Shiseido Robinson, Mohammad Mahdi Hasani-Sadrabadi.
      Autoimmune diseases encompass a diverse group of disorders with distinct clinical manifestations but a unifying defect, the breakdown of immune self-tolerance that drives dysregulated immune activation. Current therapies broadly suppress immunity rather than reestablishing regulatory balance and therefore provide limited and often transient control. Building on recent advances in nanomedicine, we introduce an immunoengineering framework that restores immune balance by delivering antigens, co-signals, and tissue repair cues with spatial and temporal precision. This review systematically examines synthetic (liposomes, polymeric nanoparticles, 2D materials), biologically derived and bioinspired (extracellular vesicles, bacterial/viral and cell-membrane vesicles), and hybrid systems, outlining design rules including size and shape, surface chemistry and ligand valency, cargo architecture, and stimuli responsiveness, that govern biodistribution, cellular uptake, and immune programming. Mechanistic principles are illustrated across distinct contexts (e.g., alloantigen responses, mucosal barrier failure, β-cell autoimmunity), emphasizing strategies that induce antigen-specific tolerance, reprogram innate compartments, and repair barriers while preserving protective immunity. We also map key translational needs: standardized characterization and potency assays, long-term safety and biodistribution, scalable manufacturing, regulatory fit, and cost-effectiveness. Together, these insights provide a blueprint for precision nanomedicine to move autoimmunity treatment from blanket suppression toward durable, mechanism-based remission.
    Keywords:  Autoimmune disease; Bioinspired nanoplatforms; Immune tolerance; Immunoengineering; Nanomedicine
    DOI:  https://doi.org/10.1016/j.jconrel.2026.115083
  65. NPJ Biofilms Microbiomes. 2026 Jun 11.
    Parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation patterns and autism-like behaviors in offspring.
    Bin Chen, Qinghua Wang, Xinxin Xue, Xin Jiang, Meilu Zhang, Changying Zhao, Chuandi Jin, Kaile Yue, Guoping Zhao, Yanan Liu, Ning Li, Lei Zhang.
      Autism spectrum disorder (ASD) is a complex neurodevelopmental condition arising from interactions between genetic and environmental factors. The interplay between the microbiota-gut-brain axis and epigenetics has been implicated in ASD, but the extent of their impact remains unclear. We hypothesized that parental gut microbiota dysbiosis shapes cross-generationally shared DNA methylation patterns and ASD-like phenotypes in offspring. Antibiotic-treated adult mice were colonized with fecal microbiota from children with ASD or typically developing (TD) controls, then bred. Colonization with ASD-associated microbiota did not alter parental behavior but induced ASD-like behavioral changes in offspring, accompanied by colonic inflammation and neuronal loss in the hippocampus and striatum. Targeted bisulfite sequencing revealed that ASD-associated microbiota reshaped methylation at ASD-related CpG sites in parental brain, blood, and colon, with a subset of these alterations also observed in offspring tissue. Integrative analyses revealed sex-specific networks linking gut microbes, DNA methylation, gene expression, metabolites, and behavior. These findings support a model in which parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation changes linked to ASD-like phenotypes in offspring. Together, these results provide novel microbial and epigenetic insights into ASD-related risk and offering a plausible mechanistic explanation for the clinical phenomenon in which unaffected parents give rise to children with ASD.
    DOI:  https://doi.org/10.1038/s41522-026-01041-4
  66. Environ Sci Pollut Res Int. 2026 Jun 08.
    Bio-inspired stearic acid functionalized polylactic acid nanofibers with nanodome architecture for enhanced oil-water separation.
    Neha Soni, Sheril Delma Vas, Tushar Kumeria, Ranu Nayak.
      Growing environmental risks from oil spills and pressing demand for sustainable oil-water separation solutions underscore an urgent need for eco-friendly, efficient, and cost-effective sorbent materials. In this study, we developed superhydrophobic nanofibers for rapid and efficient oil-water separation through surface modification with stearic acid. Polylactic acid (PLA) pellets were covalently grafted with stearic acid to introduce long-chain alkyl groups by Steglich-like esterification, followed by air-spray nebulization of the surface functionalized PLA to fabricate extremely light-weight nanofibrous sorbents with enhanced properties. Stearic acid modification significantly enhanced the hydrophobicity, surface roughness, and oleophilicity of the PLA nanofibers, resulting in superior oil sorption performance. Morphological and structural analyses (scanning electron microscopy, atomic force microscopy, and Brunauer-Emmett-Teller) confirmed the formation of nanodome-like structures on the surface of the nanofibers, that contributed to strong water repellency. The engineered nanofibers exhibited remarkable oil adsorption performance across various petroleum products and edible oil, including both heavy and light oils. Diesel uptake capacity reached 65 g g-1, far surpassing that of unmodified PLA nanofibers (14.3 g g-1). Wettability studies revealed a clear transition from hydrophobic (130° ± 2°) to superhydrophobic (151° ± 2°) phase upon surface modification. The PLA-SA-grafted nanofibers maintained robust oil sorption performance across a broad pH range (3-11), demonstrating excellent stability under varying environmental conditions. This surface modification strategy presents a promising approach for developing biodegradable, high-performance nanofibrous sorbents with strong potential for practical oil-water separation applications.
    Keywords:  Biodegradable polymer; Fatty acid; Oil spill management; Spray nebulization; Surface functionalization
    DOI:  https://doi.org/10.1007/s11356-026-37883-w
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