bims-engexo 2026-07-26 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–07–26
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Oral delivery of anti-mCD80 nanobody-engineered probiotic bacterial nanovesicles for macrophage-targeted Il17ra silencing in colitis.
Engineered Extracellular Vesicles As a New Delivery Platform for Migraine.
Target therapeutic exploitation of engineered exosome-mediated delivery of ncRNAs in cancer.
Mesenchymal Stem/Stromal Cells-Derived Exosomal Micro-RNA Delivery Enhances Bone Repair in Osteoporotic Conditions.
Liposome-extracellular vesicle hybrid nanocarriers: design principles, interfacial properties and translational perspectives.
A clinical data- and AI-supported engineered fusion vesicle system for enhanced tumor-targeted drug delivery and immunochemotherapeutic synergy.
Osteogenic peptide-engineered Coptis chinensis-derived extracellular vesicles promote immuno-osteogenic repair of diabetic bone defects.
Surface charge engineering shields extracellular vesicles from plasma protein corona to enable systemic extrahepatic targeting.
Exosome-Loaded Zinc Sulfide Nanoparticles Therapy for Psoriasis: Immune Regulation and Skin Repair by Targeting IL-23/IL-17A-NF-κB Pathway.
Energy-assisted CRISPR cleavage and probiotic vesicle signaling platform: Microbiome reprogramming for homeostasis.

J Nanobiotechnology. 2026 Jul 21.

Oral delivery of anti-mCD80 nanobody-engineered probiotic bacterial nanovesicles for macrophage-targeted Il17ra silencing in colitis.

Manli Zhang, Yonggang Zhu, Feng Hu, Min Rao.

  Inflammatory bowel disease remains challenging to treat because effective intervention requires localized suppression of mucosal inflammation together with restoration of tissue homeostasis. Here, a hierarchically engineered oral nanotherapeutic is developed based on Lactobacillus rhamnosus GG-derived bacterial nanovesicles (BNVs) for inflammatory macrophage-targeted gene silencing in colitis. The vesicles are genetically engineered to display an anti-mCD80 nanobody, loaded with siIl17ra, and further encapsulated within calcium alginate microcapsules to improve gastrointestinal protection and enable gastrointestinal protection and intestinal-fluid-associated release in the lower gut. The resulting system preserves nanoscale vesicular morphology, exhibits favorable cytocompatibility, and shows enhanced uptake by inflammatory macrophages after nanobody decoration. Following internalization, siIl17ra/CD80-BNVs effectively suppress Il17ra expression and reprogram macrophages toward a pro-repair phenotype. Microcapsule incorporation further improves siRNA retention, restrains premature release under acidic conditions, and promotes sustained release under intestinally relevant pH conditions. After oral administration, MC-siIl17ra/CD80-BNVs display enhanced colorectal retention and markedly alleviate dextran sulfate sodium-induced colitis, as evidenced by reduced disease activity, attenuated histopathological injury, enhanced epithelial regeneration, decreased inflammatory mediator expression, and reduced NF-κB/caspase-associated marker changes. This work establishes a microbiota-inspired oral nanomedicine platform for localized immunomodulation and mucosal repair in colitis.

Keywords:  Bacterial nanovesicles; Inflammatory bowel disease; Macrophage targeting; Oral nanomedicine; SiRNA delivery

DOI:  https://doi.org/10.1186/s12951-026-04811-6
ACS Appl Bio Mater. 2026 Jul 22.

Engineered Extracellular Vesicles As a New Delivery Platform for Migraine.

Abhirami Subramony, Vinay Kumar Patel, Siva Syam Kumar, Sreeja C Nair.

  Migraine represents a complex neurovascular disorder that is challenging to treat due to the blood-brain barrier (BBB) and complex pathophysiology involving the trigeminovascular system, neuroinflammation, and cortical spreading depression. Current systemic therapies, including calcitonin gene-related peptide (CGRP) inhibitors, offer benefits but have limited efficacy and may cause adverse effects; thus, highlighting the need for targeted delivery across the BBB. This review introduces extracellular vesicles (EVs) as an appropriate pharmaceutical engineering platform to address such challenges. While traditional treatments have inherent disadvantages, engineered EVs offer efficient blood-brain barrier (BBB) penetration, targeted delivery, and multi-therapeutic payload capacity for migraine-associated neural circuits. We introduce a framework for pathophysiology-informed technology by first discussing the role of native EVs in promoting the migraine cascade to identify specific sites of therapeutic intervention. In this review, the focus is on pharmaceutical nanotechnology, starting with the strategic selection of producer cells, including "Hijack & Modify" vs De Novo Design, and continuing through sequential nano-engineering of EVs by surface functionalization and utilization of hybrid vesicles for targeting the BBB and trigeminovascular systems to state-of-the-art smart-release systems. We continue with the critical analytical and manufacturing sciences needed to translate such engineered EVs from bench to bedside, addressing important translational challenges through scalable Good manufacturing practices (GMP) production, supported potency assays, and comprehensive quality assurance processes. These include potency tests, GMP production, and robust quality control that may be expanded. Finally, we combine all of these into a single translational pathway that examines the regulatory issues, the patent landscape, and the future of personalized EV therapeutics. The current review provides an exhaustive framework for developing EV-based treatments by combining cutting-edge pharmaceutical nanotechnology with deep biological insights to make migraine treatment more reliable.

Keywords:  blood-brain barrier; extracellular vesicles; migraine; nano-engineering; translational medicine; trigeminovascular system

DOI:  https://doi.org/10.1021/acsabm.6c00833
Cancer Gene Ther. 2026 Jul 21.

Target therapeutic exploitation of engineered exosome-mediated delivery of ncRNAs in cancer.

Fatemeh Chaharlang, Nafiseh Mahdipour, Sana Alizadeh Rami, Parichehr Angouti, Alireza Ahmadi, Mohammad Khalaj-Kondori.

Non-coding RNAs, as microRNAs, long non-coding RNAs, and circular RNAs, are significant modulators of tumor biology and gene expression. miRNAs primarily regulate gene expression at the post-transcriptional level, whereas lncRNAs influence transcriptional activity and epigenetic states. Moreover, circRNAs function as highly stable molecules that shape oncogenic pathways by sequestering miRNAs and interacting with RNA-binding proteins. By addressing these regulatory roles, ncRNAs have emerged as attractive candidates for therapeutic intervention, yet their clinical translation remains limited by rapid degradation, insufficient cellular uptake, and off-target effects. Engineered exosomes-natural nanosized vesicles with strong biocompatibility and barrier-crossing capacity-represent a promising platform to overcome these delivery challenges. This review provides a comprehensive overview of recent advances in exosome engineering for cancer-directed ncRNA delivery. We summarize state-of-the-art strategies designed to enhance loading efficiency, targeting specificity, and therapeutic performance of exosome-mediated delivery systems for miRNAs, lncRNAs, and circRNAs, and outline their growing potential in next-generation cancer therapy.

DOI: https://doi.org/10.1038/s41417-026-01059-y
Tissue Eng Part A. 2026 Jul 21. 19373341261471040

Mesenchymal Stem/Stromal Cells-Derived Exosomal Micro-RNA Delivery Enhances Bone Repair in Osteoporotic Conditions.

Subhasis Mandal, Lauren Kim, Minjee Kang, Iram Elamin, Meghna Rao, Ishraga S Elsayed, Changlu Xu, Tara L Aghaloo, Min Lee, Jiabing Fan.

  Osteoporosis-associated bone fractures are a leading cause of disability in the elderly population. Developing effective therapeutic strategies to enhance bone repair under osteoporotic conditions remains a major clinical challenge. Increasing evidence indicates that aberrant lineage commitment of mesenchymal stem/stromal cells (MSCs) resident in bone marrow contributes to osteoporosis-related bone loss. However, incomplete understanding of the regulatory mechanisms governing MSC differentiation has limited the development of efficient therapeutic approaches. In this study, we identified micro-RNA-423 (miR-423) as a negative regulator of osteogenic differentiation, and demonstrated that inhibition of miR-423 significantly enhanced osteoblast differentiation of MSCs. To enable in vivo delivery of the miR-423 inhibitor for bone repair, MSC-derived exosomes (MSC-Exo) were used as a delivery vehicle, generating the Exo-miR-423 inhibitor construct. These exosomes were subsequently incorporated into an apatite-coated poly(lactic-co-glycolic acid) scaffold to form an Exo-miR-423 inhibitor/scaffold complex. Implantation of this complex significantly promoted bone healing in a calvarial defect model in ovariectomized mice. Collectively, these findings demonstrate a promising miRNA-modulated, exosome-based tissue engineering strategy for enhancing bone defect and fracture repair under osteoporotic conditions, and highlight its potential for further optimization and translational application.

Keywords:  MSC-derived exosomes; bone repair; miR-423; osteoporotic condition

DOI:  https://doi.org/10.1177/19373341261471040
Biomater Sci. 2026 Jul 22.

Liposome-extracellular vesicle hybrid nanocarriers: design principles, interfacial properties and translational perspectives.

Jingyi Huang, Shijie Fu, Wanjiao Chen, Baojuan Li, Hang Chen, Xinmei Chen, Zhizhe Lin, Youfa Xu, Xin Wu.

Liposome-extracellular vesicle (EV) hybrid nanocarriers have emerged as a versatile strategy to integrate the physicochemical tunability of synthetic liposomes with the biological functionality of EV membranes. However, a materials-oriented understanding of how membrane fusion alters supramolecular organization and interfacial behavior remains insufficient. Despite extensive reports of enhanced drug loading, cellular uptake and therapeutic efficacy, systematic understanding of how membrane fusion alters interfacial properties and subsequent biological responses remains limited. Fusion-induced changes in lipid organization, membrane rigidity and protein distribution may significantly affect colloidal stability, receptor-mediated interactions and immune compatibility. This review provides a comprehensive overview of contemporary engineering strategies for liposome-EV hybrid systems, emphasizing the core design principles that govern their structural integrity, functional performance, and safety. By correlating membrane architecture with nano-bio interfacial dynamics, we propose a multidimensional evaluation framework that bridges physicochemical characteristics with biological outcomes. Ultimately, this analysis seeks to provide a roadmap for the rational engineering of hybrid vesicles, ensuring their enhanced clinical and translational relevance.

DOI: https://doi.org/10.1039/d6bm00356g
J Control Release. 2026 Jul 22. pii: S0168-3659(26)00598-5. [Epub ahead of print] 115195

A clinical data- and AI-supported engineered fusion vesicle system for enhanced tumor-targeted drug delivery and immunochemotherapeutic synergy.

Wenliang Yu, Xiaohui Bai, Chenyang Li, Xiaoran Zhou, Te Yin, Yihan Xiao, Yao Li, Lin Sun, Ziyi Tan, Yuning Meng, Yanze Ma, Zichun Hua.

  Cell- or bacteria-derived membrane vesicles (MVs) serve as platforms for delivering antitumor small-molecule drugs, characterized by targeted delivery, immunostimulatory activity, and ease of engineering. Despite extensive innovative research, clinical translation remains limited. Here, we report a clinically data- and AI- supported engineered fusion vesicle delivery system, ECMVRGD. The design was supported and guided by a systematic meta-analysis identifying clinically safe and potentially effective RGD peptides and AI molecular dynamics simulations to determine optimal insertion sites and copy numbers (one RGD [RGD4C] each at Loop 2 and Loop 3 of OmpA) on a previously validated safe and effective engineered membrane vesicle (EMV) platform, which was further fused with cancer cell-derived membrane vesicles (CMVs). This engineering strategy not only places translational potential at the forefront from the outset but also when loaded with doxorubicin (DOX), demonstrates comprehensive improvements over CMV in both tumor-targeted delivery and antitumor immune activation in vitro and in vivo. Mechanistic studies further revealed that ECMVRGD@DOX achieved complete recurrence-free antitumor immunochemotherapeutic efficacy (0/6 recurrence) by synergistically promoting dendritic cell (DC) activation and CD8+ T cell infiltration. This engineered fusion vesicle platform provides a novel strategy to advance the design of MVs-based delivery systems with improved translational potential.

Keywords:  AI simulations; Drug delivery; Engineered fusion vesicles; Immunochemotherapy; meta-analysis

DOI:  https://doi.org/10.1016/j.jconrel.2026.115195
Colloids Surf B Biointerfaces. 2026 Jul 21. pii: S0927-7765(26)00591-6. [Epub ahead of print]268(Pt 1): 116003

Osteogenic peptide-engineered Coptis chinensis-derived extracellular vesicles promote immuno-osteogenic repair of diabetic bone defects.

Jie Gao, Li Li, Bin Hu, Yukang Que, Yong Hu.

  Diabetic bone defects are difficult to repair because chronic hyperglycemia creates a hostile inflammatory and oxidative microenvironment that impairs osteogenesis, enhances osteoclast activity and compromises vascular ingrowth. Plant-derived extracellular vesicle-like nanoparticles can transfer source-related biological signals to mammalian cells and are attractive for immune regulation, but native vesicles usually lack defined osteogenic instruction for diabetic bone regeneration. Here, we engineered Coptis chinensis-derived extracellular vesicle-like nanoparticles (Cc-EVs) with a BMP-2-derived osteogenic peptide (OP) through copper-free click chemistry, generating OP-Cc-EVs that combine the immunoregulatory potential of Cc-EVs with osteogenic peptide surface presentation. As a vesicle-only treatment in vitro, OP-Cc-EVs shifted inflammatory macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype, with transcriptomic changes consistent with inflammatory resolution and repair-oriented tissue regulation. This macrophage response enhanced mesenchymal stromal cell osteogenesis, suppressed osteoclast formation and actin-ring maturation, and generated paracrine signals that promoted endothelial migration and tube formation. For in vivo application, GelMA hydrogel was used as a local carrier to retain OP-Cc-EVs within the diabetic bone-defect site. In a diabetic femoral condyle defect model, local delivery of OP-Cc-EVs promoted vascularized bone regeneration while reducing inflammatory and osteoclastic signals. These findings establish OP-Cc-EVs as a chemically engineered plant-derived vesicle platform with translational potential for immuno-osteogenic repair of diabetic bone defects.

Keywords:  Angiogenesis; Bone regeneration; Copper-free click chemistry; Coptis derived extracellular vesicles; Immuno-osteogenesis

DOI:  https://doi.org/10.1016/j.colsurfb.2026.116003
Mater Today Bio. 2026 Aug;39 103471

Surface charge engineering shields extracellular vesicles from plasma protein corona to enable systemic extrahepatic targeting.

Taotao Tang, Mengyun Wang, Xiaowei Xu, Jin Wang, Yan Wang, Fangzhou Wang, Deping Wu, Yilin Zhang, Shuangshuang Liu, Lingting Kong, Zhiqing Chen, Feng Chen, Yi Wen, Bin Wang, Junjia Wang, Bicheng Liu, Linli Lv.

  The plasma protein corona (PC) critically influences the in vivo fate of nanomedicines, yet its composition and impact on extracellular vesicles (EVs) remain poorly defined. Using a biomimetic circulation system, we characterized PC formation and modulation on two clinically relevant EV types: mesenchymal stromal cell-derived EVs (MSC-EVs) and HEK293F-derived EVs (293F-EVs). Under dynamic flow, both EV types acquired stable coronas, resulting in increased particle size and decreased surface charge. Proteomic profiling revealed a shared corona signature enriched in immunoglobulins, complements, and other plasma components. Functionally, PC formation enhanced macrophage uptake and triggered inflammatory activation, primarily via interactions between corona-bound immunoglobulins or complement C3 and their respective receptors. To disrupt this process, we developed a charge-shielding strategy using positively charged chitosan oligosaccharide (COS) to inhibit PC assembly. COS coating effectively neutralized EV surface charge and reduced opsonin adsorption and non-specific macrophage clearance, thereby reshaping EV biodistribution-limiting hepatic sequestration and enhancing delivery to extrahepatic organs. In a murine sepsis model, COS-modified MSC-EVs further improved renal and pulmonary outcomes and markedly increased survival. Collectively, these findings elucidate the molecular architecture and immunological impact of the EV-associated plasma PC and introduce a promising anti-corona strategy for engineering stealthier and more effective EV-based nanotherapeutics.

Keywords:  Chitosan oligosaccharide; Extracellular vesicles; Mesenchymal stem cell; Protein corona; Surface charge

DOI:  https://doi.org/10.1016/j.mtbio.2026.103471
J Drug Target. 2026 Jul 22. 1-25

Exosome-Loaded Zinc Sulfide Nanoparticles Therapy for Psoriasis: Immune Regulation and Skin Repair by Targeting IL-23/IL-17A-NF-κB Pathway.

Neveen A Salem, Noha A Mowaad, Rania Elgohary, Asmaa Osama B S Osman, Mohamed Reda, Mohamed S Kishta.

  This study investigates the therapeutic efficacy of zinc sulfide nanoparticles (ZnS NPs) encapsulated within adipose-derived mesenchymal stem cell exosomes (EXO-ZnS NPs) in an imiquimod-induced rat model of psoriasis, aiming to combine nanotechnology and regenerative medicine for enhanced immune modulation and skin repair. Adipose mesenchymal stem cells (AD-MSCs) were cultured and characterized, exosomes were isolated and validated by flow cytometry and TEM. ZnS NPs were synthesized, confirmed by XRD and TEM, and encapsulated into exosomes. Release profiles, Clinical (PASI scoring), histopathological, inflammatory and proliferative markers as well as immunohistochemical analyses were evaluated across control, psoriasis, and treatment groups (EXO, ZnS NPs, and EXO-ZnS NPs). EXO-ZnS NPs exhibited a uniform nanosize with sustained ZnS NPs release (80.5% over 24 h). In vivo, EXO-ZnS NPs significantly attenuated psoriatic symptoms, and Severity Index scores, reduced inflammatory mediators (IL-23, IL-17a, TNF-α, MCP-1, NLRP3), mitigated oxidative stress, downregulated proliferative markers (Ki-67, MMP-9), and inhibited VEGF-mediated angiogenesis. collectively restored epidermal structure and improved skin architecture. EXO-ZnS NPs synergistically combine the regenerative and immunomodulatory effects of exosomes with the intrinsic anti-inflammatory and antioxidant activities of ZnS NPs, offering a novel promising, dual-action therapeutic platform for effective and sustained psoriasis management.

Keywords:  Exosomes; Inflammation; Mesenchymal Stem Cells; Psoriasis; Zinc Sulfide Nanoparticles

DOI:  https://doi.org/10.1080/1061186X.2026.2708742
Sci Adv. 2026 Jul 24. 12(30): eaef1760

Energy-assisted CRISPR cleavage and probiotic vesicle signaling platform: Microbiome reprogramming for homeostasis.

Zilin Zhou, Yingming Yang, Fangjie Zhou, Kunneng Liang, Tao Gong, Xinxuan Zhou, Jianshu Li, Jun Luo, Jiyao Li, Jiaojiao Yang.

Pathogenic infections drive microbial dysbiosis and persistent inflammation, posing therapeutic challenges due to difficulties in precise pathogen eradication and microbiome restoration. Although CRISPR-based therapeutics enable pathogen-specific antibacterial targeting, their effectiveness in treating pathogenic infections is constrained by difficulties in navigating complex microbial ecosystems, penetrating pathogenic barriers, sustaining energy-intensive intracellular cleavage, and, critically, restoring microbial balance after pathogen clearance. Here, we engineer a probiotic vesicle-synergized CRISPR platform by encapsulating gtfB-targeting CRISPR plasmids within hybrid extracellular vesicles from probiotics and pathogenic Streptococcus mutans. The pathogen-derived vesicle component enables targeted uptake by S. mutans, facilitating intracellular cleavage of the virulence gene gtfB. Vesicle-carried endogenous adenosine triphosphate (ATP) boosts CRISPR activity, amplifying targeted DNA cleavage for potent and selective pathogen elimination. Probiotic-derived vesicle components further remodel quorum-sensing networks and immunity, restoring microbial homeostasis. This probiotic vesicle-based strategy integrates ATP-enhanced CRISPR cleavage with microbiome and immune modulation, offering a next-generation therapeutic paradigm for microbiome-associated diseases.

DOI: https://doi.org/10.1126/sciadv.aef1760