bims-engexo 2026-03-01 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–03–01
fifteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered Exosomes: Advances in Therapeutic Applications for Otolaryngology-Head and Neck Diseases.
Anti-CD19 engineered exosomes enable B-cell targeted anti-BAFF mRNA delivery to alleviate lupus progression.
Engineered Exosomes Co-Delivering EGF and FGF Ameliorate Androgenetic Alopecia in a Mouse Model.
Exosomes as Specific Vehicles for Delivery of Combination Therapies for Inhibiting Autophagy and Inducing Apoptosis in MYCN-Amplified Neuroblastoma Displaying Gut Dysbiosis: Current Challenges and Future Opportunities.
Exosome Augmentation Technologies for Drug Delivery and Disease Treatment: A Review.
How Effective are Exosomes in Overcoming Blood-Labyrinth Barrier in Sensorineural Hearing Loss? A Comprehensive Review of the Literature.
Controlling Biogenesis and Engineering of Exosomes to Inhibit Growth and Promote Death in Glioblastoma Multiforme.
Construction of Curcumin-Loaded Mesenchymal Stem Cell-Derived Exosomes and Their Mechanism in Inhibiting Pyroptosis During Hepatic Ischemia-Reperfusion Injury.
Red Blood Cell-Derived Extracellular Vesicles for Gene and RNA Therapeutics: Biological, Engineering, and Translational Challenges.
Engineering integrin αvβ8-targeted extracellular vesicles to deliver BDNF mRNA for motor recovery in spinal cord injury.
Mesenchymal stem cell-derived exosomes in myocardial infarction repair: therapeutic potential and scaffold-based delivery strategies.
[Preparation of bacterial outer membrane vesicles modified with anti-angiogenic peptide AP25 on the surface and evaluation of their anti-tumor effects].
A Single-Center, Open-Label Study to Evaluate the Efficacy and Tolerability of Retinal Encapsulated in a Novel Biomimetic Exosome in the Treatment of Mild-To-Moderate Facial Photodamage.
Sirt3 Genetically Engineered Apoptotic Bodies Alleviate Skeletal Aging by Limiting Aggravated NLRP3 Inflammasome Activation of Senescent Macrophages.
Bioorthogonal and synthetic biology-engineered bacterial outer membrane vesicles for enhanced photo-immunotherapy.

Int J Nanomedicine. 2026 ;21 574708

Engineered Exosomes: Advances in Therapeutic Applications for Otolaryngology-Head and Neck Diseases.

Han Zhu, Jing He, Shishi Yang, Gang Qin.

  Given the intricate anatomy of otolaryngology-head and neck (OHNS) regions and the inherent limitations of conventional therapies, many OHNS diseases have suboptimal clinical outcomes. As natural intercellular mediators, exosomes have demonstrated unique application potential in OHNS treatment in recent years, thanks to their high biocompatibility, low immunogenicity, and intrinsic targeting capabilities. However, such issues as limited drug-loading capacity, suboptimal in vivo stability, and insufficient targeting precision still hinder their clinical translation. Notably, recent advances in engineering strategies such as genetic editing, surface modification, and optimized drug loading enhance natural exosomes' functionality, boosting targeting accuracy, in vivo stability, and therapeutic efficacy. Considering conventional therapy limitations and engineered exosomes' unique potential, this review synthesizes their progress, mechanisms, and translational challenges in OHNS, and addresses lingering technical and translation barriers via interdisciplinary collaboration to optimize their design, utility, and bench-to-bedside translation, as these exosomes are promising precision tools for refractory OHNS diseases advancing precision medicine in the field.

Keywords:  engineered exosomes; inflammatory diseases; otorhinolaryngological tumors; targeted delivery; tissue regeneration and repair

DOI:  https://doi.org/10.2147/IJN.S574708
Mol Ther. 2026 Feb 24. pii: S1525-0016(26)00080-8. [Epub ahead of print]

Anti-CD19 engineered exosomes enable B-cell targeted anti-BAFF mRNA delivery to alleviate lupus progression.

Linda Zeng, Jingxian Shu, Shuping Zhong, Xin Dong, Yongjian Wu, Xi Huang.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by abnormal activation of B cells. Excessive B-cell activating factor (BAFF) of the tumor necrosis factor family plays an essential role in B-cell hyperactivation. Blocking the binding of excessive BAFF to its receptors is becoming a promising approach for SLE treatment. Here, we constructed genetically engineered exosomes derived from HEK293 cells that were functionalized with anti-CD19 (a B-cell-specific surface marker) and loaded with anti-BAFF mRNA (CD19@Anti-BAFFmRNA Exo). The anti-CD19 modification mediated receptor-dependent targeted binding and internalization, ensuring precise delivery of anti-BAFF mRNA to B cells. This enabled B cells to produce anti-BAFF antibodies in vivo, which captured excess BAFF, thereby inhibiting abnormal B-cell activation and proliferation. Notably, mice with lupus treated with CD19@Anti-BAFFmRNA Exo exhibited alleviated kidney damage and reduced disease progression. Our B-cell-targeted engineered exosomes loaded with anti-BAFF mRNA provide a novel approach to enhance antibody production and improve local antibody concentration, offering a potential therapeutic strategy for SLE.

DOI: https://doi.org/10.1016/j.ymthe.2026.01.037
Int J Nanomedicine. 2026 ;21 572518

Engineered Exosomes Co-Delivering EGF and FGF Ameliorate Androgenetic Alopecia in a Mouse Model.

Yongxian Lai, Junchao Wu, Tianhao Tan, Bo Gao, Jie Han, Zhongmin Liu, Xiaofeng Ding.

   Background: Androgenetic alopecia (AGA) is characterized by hair follicle miniaturization and growth factor deficiency. However, conventional therapies such as minoxidil and finasteride fail to restore the pathological follicular microenvironment, highlighting the urgent need for novel therapeutic strategies. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) are key regulators of hair follicle regeneration, yet their expression is downregulated in the follicular microenvironment of AGA patients.
Methods: This study validated the expression profile of growth factors in hair follicles of AGA patients through clinical sample analysis. Subsequently, dual‑factor engineered exosomes (EXO‑EGF/FGF) loaded with EGF and FGF were constructed using LAMP2B fusion engineering technology with 293T cells as donor cells. EXO‑EGF/FGF was characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The regulatory effects of EXO‑EGF/FGF on human dermal papilla cells (HDPCs) were evaluated in vitro. An androgen‑induced AGA mouse model was established to assess the therapeutic efficacy and safety of EXO‑EGF/FGF in vivo.
Results: Clinical sample analysis confirmed that the expression of EGF and FGF was significantly downregulated in dermal papilla cells of AGA patients, leading to reduced expression of NOTCH signaling pathway proteins associated with hair follicle regeneration. TEM and NTA results demonstrated that EXO‑EGF/FGF exhibited exosomal morphology, with significantly higher expression levels of EGF and FGF than natural exosomes. In vitro experiments revealed that EXO‑EGF/FGF promoted the proliferation and migration of HDPCs by reactivating the cell cycle and enhancing migration‑related programs. In the AGA mouse model, EXO‑EGF/FGF effectively restored hair coverage density and follicular structural integrity without inducing immunogenic reactions or systemic toxicity, and significantly increased the number of anagen‑phase hair follicles in post‑treatment tissues.
Conclusion: This study demonstrated that LAMP2B‑engineered EXO‑EGF/FGF acted on follicular cells to repair the pathological microenvironment in AGA. This strategy overcame the inherent limitations of conventional therapies and natural exosomes, offering a novel, safe, and clinically translatable therapeutic approach for AGA treatment.

Keywords:  androgenetic alopecia; clinical translation; engineered exosomes; follicular microenvironment; growth factor

DOI:  https://doi.org/10.2147/IJN.S572518
Brain Sci. 2026 Jan 24. pii: 125. [Epub ahead of print]16(2):

Exosomes as Specific Vehicles for Delivery of Combination Therapies for Inhibiting Autophagy and Inducing Apoptosis in MYCN-Amplified Neuroblastoma Displaying Gut Dysbiosis: Current Challenges and Future Opportunities.

Kendall Leigh, Swapan K Ray.

  Neuroblastoma is a highly aggressive pediatric malignancy originating from neural crest progenitor cells, predominantly in the adrenal medulla. Amplification of the MYCN oncogene occurs in 20-30% of all neuroblastoma cases and approximately 50% of high-risk tumors, strongly correlating with poor prognosis, relapse, and multidrug resistance. MYCN-driven oncogenesis promotes tumor progression by suppressing apoptotic signaling and enhancing survival pathways, including autophagy-a key mechanism underlying resistance to chemotherapy and immunotherapy. This review examines current therapeutic strategies and resistance mechanisms in MYCN-amplified neuroblastoma, while introducing emerging approaches utilizing exosomes as precision drug delivery systems. Exosomes, nanoscale extracellular vesicles secreted by the tumor cells, exhibit natural tropism and can be engineered to selectively target neuroblastoma-specific biomarkers such as glypican-2 (GPC2), which is highly expressed in MYCN-amplified tumors. Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine-an FDA-approved autophagy inhibitor-to simultaneously inhibit autophagy and induce apoptotic signaling. This dual-targeted approach aims to overcome drug resistance, reduce off-target toxicity, and enhance therapeutic efficacy through exosome-mediated specificity. Furthermore, gut dysbiosis has emerged as a critical factor influencing tumor progression and diminishing treatment efficacy in MYCN-amplified neuroblastoma. We propose integrating microbiota-derived exosomes engineered to deliver anti-inflammatory microRNAs (miRNAs) to the gut mucosa, restoring eubiosis and potentiating systemic anti-tumor responses. Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients.

Keywords:  MYCN-amplified neuroblastoma; apoptosis; autophagy; combination therapies; engineered exosomes; gut dysbiosis

DOI:  https://doi.org/10.3390/brainsci16020125
Biomater Res. 2026 ;30 0318

Exosome Augmentation Technologies for Drug Delivery and Disease Treatment: A Review.

Jun Wu, Ruibin Li, Lu Cao, Peiqi Wang, Shiqi Jiang, Yan Chen, Haoxin Fu, Xinhao Xu, Guanyang Lin, Lanjie Lei, Ren-Ai Xu.

Exosomes are nanovesicles secreted by cells to exchange materials and information. Recent studies have revealed that these modified nanovesicles can be powerful tools for the diagnosis and treatment of diseases. However, few studies have reported on the acquisition and application of these functionalized exosomes. Therefore, this study provides a systematic summary of the entire process of isolation, functionalization, modification, and application of enhanced exosomes and recent progress in this field. First, the process of exosome production and principles of disease treatment are elucidated. Thereafter, the methods of exosome isolation are summarized, with a focus on improved technology centered on aptamer technology and new technology represented by microfluidics. Next, the functional modifications of the exosomes are classified and summarized. Finally, new breakthroughs in the diagnostic and therapeutic capabilities of function-enhancing exosomes compared with those of traditional exosomes are summarized, especially in terms of how these exosomes can be used in bioimaging, photothermal therapy, and other means of achieving a quantum leap in detection and therapeutic efficacy. This paper summarizes the latest research findings on engineered exosomes, with a particular focus on emerging technologies such as microfluidics and aptamers that hold significant potential. It provides a thorough analysis of their respective advantages and limitations, aiming to offer actionable insights for the future advancement and more complex applications of exosomes.

DOI: https://doi.org/10.34133/bmr.0318
Int J Nanomedicine. 2026 ;21 577963

How Effective are Exosomes in Overcoming Blood-Labyrinth Barrier in Sensorineural Hearing Loss? A Comprehensive Review of the Literature.

Jiawei Du, Shiyi Pan, Shiyu Qiu, Nan Cheng, Lian Chen, Ying Hu, Yongjie Wei, Yuhua Zhang, Jianming Yang, Wei Cao, Qiaojun Fang.

  Sensorineural hearing loss (SNHL) is a prevalent global health issue, and its pharmacological treatment is severely hindered by the blood-labyrinth barrier (BLB). Exosomes, natural extracellular vesicles (30-150 nm), have emerged as a highly promising nanoplatform to overcome this delivery challenge. Their innate biocompatibility, low immunogenicity, and ability to cross biological barriers make them ideal for targeted drug delivery. This review examines the inner ear barrier systems and elucidates the mechanisms, such as receptor-mediated transcytosis, by which exosomes can traverse the BLB. It further discusses engineering strategies to optimize drug loading, enhance targeting, and improve therapeutic efficacy for SNHL. The application of engineered exosomes in delivering diverse cargoes-including nucleic acids, proteins, and small-molecule drugs-is comprehensively reviewed, highlighting their potential in preclinical models to preserve auditory function. Despite this promise, significant challenges remain in standardization, scalable production, loading efficiency, long-term safety, and clinical translation. Future research should focus on refining engineering techniques, elucidating in vivo pharmacokinetics, and advancing preclinical studies to facilitate the clinical adoption of exosome-based therapies, ultimately offering a novel and precise paradigm for SNHL treatment.

Keywords:  blood-labyrinth barrier; clinical translation; drug delivery; engineered exosomes; sensorineural hearing loss

DOI:  https://doi.org/10.2147/IJN.S577963
Brain Sci. 2026 Jan 25. pii: 130. [Epub ahead of print]16(2):

Controlling Biogenesis and Engineering of Exosomes to Inhibit Growth and Promote Death in Glioblastoma Multiforme.

Srikar Alapati, Swapan K Ray.

  Glioblastoma multiforme (GBM) is characterized by aggressive growth, extensive vascularization, high metabolic malleability, and a striking capacity for therapy resistance. Current treatments involve surgical resection and concomitant radiation therapy and chemotherapy, prolonging survival times marginally due to the therapy resistance that is built up by the tumor cells. A growing body of research has identified exosomes as critical enablers of therapy resistance. These nanoscale vesicles enable GBM cells to disseminate oncogenic proteins, nucleic acids, and lipids that collectively promote angiogenesis, maintain autophagy under metabolic pressure, and suppress apoptosis. As interest grows in targeting tumor communication networks, exosome-based therapeutic strategies have emerged as promising avenues for improving therapeutic outcomes in GBM. This review integrates current insights into two complementary therapeutic strategies: inhibiting exosome biogenesis and secretion, and engineering exosomes as precision vehicles for the delivery of anti-tumor molecular cargo. Key molecular regulators of exosome formation-including the endosomal sorting complex required for transport (ESCRT) machinery, tumor susceptibility gene 101 (TSG101) protein, ceramide-driven pathways, and Rab GTPases-govern the sorting and release of factors that enhance GBM survival. Targeting these pathways through pharmacological or genetic means has shown promise in suppressing angiogenic signaling, disrupting autophagic flux via modulation of autophagy-related gene (ATG) proteins, and sensitizing tumor cells to apoptosis by destabilizing mitochondria and associated survival networks. In parallel, advances in exosome engineering-encompassing siRNA loading, miRNA enrichment, and small-molecule drug packaging-offer new routes for delivering therapeutic agents across the blood-brain barrier with high cellular specificity. Engineered exosomes carrying anti-angiogenic, autophagy-inhibiting, or pro-apoptotic molecules can reprogram the tumor microenvironment and activate both the intrinsic mitochondrial and extrinsic ligand-mediated apoptotic pathways. Collectively, current evidence underscores the potential of strategically modulating endogenous exosome biogenesis and harnessing exogenous engineered therapeutic exosomes to interrupt the angiogenic and autophagic circuits that underpin therapy resistance, ultimately leading to the induction of apoptotic cell death in GBM.

Keywords:  angiogenesis; apoptosis; autophagy; exosome biogenesis and engineering; glioblastoma multiforme (GBM); therapy resistance

DOI:  https://doi.org/10.3390/brainsci16020130
Pharmaceuticals (Basel). 2026 Feb 10. pii: 296. [Epub ahead of print]19(2):

Construction of Curcumin-Loaded Mesenchymal Stem Cell-Derived Exosomes and Their Mechanism in Inhibiting Pyroptosis During Hepatic Ischemia-Reperfusion Injury.

Xinyu Dong, Lei Sun, Die Hu, Wei He, Yunjian Pan, Ruihua Wang, Xinrui Lin, Zhe Jiang, Xuekun Xing.

  Objective: Hepatic ischemia-reperfusion injury (HIRI) is a common pathological condition in liver surgery and transplantation, and cellular pyroptosis plays a key role in its pathogenesis. However, the clinical application of curcumin is limited by its poor water solubility and low bioavailability. This study aims to develop mesenchymal stem cell (MSC)-derived exosomes loaded with curcumin (Exo-Cur). It also investigates the role and mechanism of Exo-Cur in inhibiting HIRI-related cellular pyroptosis. Methods: The preparation of Exo-Cur was optimized using orthogonal experimental design. Its solubility, stability, particle size distribution, and zeta potential were then evaluated. The morphology of Exo-Cur and its uptake in hepatocytes were observed using laser scanning confocal microscopy. The effect of Exo-Cur on HIRI was assessed through hematoxylin and eosin (HE) staining, ALT and AST measurements, TUNEL assay, CCK-8 assay, and lactate dehydrogenase (LDH) assay. Inflammatory cytokine protein levels were quantified by ELISA, and their mRNA expression was assessed by qRT-PCR. Pyroptosis was assessed by Western blot, immunohistochemistry, and flow cytometry. Additionally, protein expression changes in the PI3K/Akt/mTOR signaling pathway were analyzed using Western blot. Results: Orthogonal experiments determined that the optimal preparation method for Exo-Cur involves cell density at 95%, a curcumin concentration of 30 μg/mL, and a co-cultivation time of 12 h. Characterization results showed that Exo-Cur maintained its typical cup-shaped structure as well as stable particle size and zeta potential. Additionally, its water solubility and its stability in vitro were significantly improved compared to free curcumin. Further mechanistic studies indicated that Exo-Cur could ameliorate the abnormal morphology resulting from HIRI-induced hepatocyte pyroptosis, reduce the proportion of pyroptotic cells, and significantly downregulate the expression of NLRP3 inflammasome and downstream pyroptosis-related proteins (ASC, C-Caspase-1, GSDMD-N). Pathway analysis revealed that Exo-Cur activates the PI3K/Akt/mTOR axis, a pathway inhibited by HIRI. Moreover, rapamycin, an inhibitor of this pathway, reverses Exo-Cur's anti-pyroptosis effect. Conclusions: This study develops an efficient and stable Exo-Cur delivery system, confirming its protective effect against HIRI by activating the PI3K/Akt/mTOR axis and inhibiting NLRP3-mediated cellular pyroptosis. This innovative combination of MSC-derived exosomes combined with curcumin overcomes the limitations in clinical application of curcumin, such as poor bioavailability and stability, and offers a novel nanotherapeutic strategy to treat HIRI clinically.

Keywords:  curcumin; exosomes; hepatic ischemia–reperfusion injury; mesenchymal stem cell; pyroptosis

DOI:  https://doi.org/10.3390/ph19020296
Int J Nanomedicine. 2026 ;21 579975

Red Blood Cell-Derived Extracellular Vesicles for Gene and RNA Therapeutics: Biological, Engineering, and Translational Challenges.

Tayyab Shafiq, Nawaz Khan, Tehreem Kausar, Waqas Ahmed, Zihao Zhang, Yujie Liang, Li Duan.

  Gene therapy has great prospects of DNA/RNA manipulations and protein modulations. Its use in clinic is, however, stifled by risks of immunogenicity, low target specificity, and adverse effects. The red blood cell (RBC-EVs) extracellular vesicles can serve as a solution to this issue since they are biocompatible, long-term stable, and with low immunogenicity. RBC-EVs permit the accurate delivery of therapeutic cargo to space and time, thus minimizing systemic toxicity. This review presents the most recent developments on the expansion of the use of RBC-EVs to encapsulate the components of mRNA and CRISPR-Cas. Through the addition of the means to address these deficiencies, including stimulus-sensitive release mechanisms (eg, pH- or light-activated systems) and tissue-selective targeting approaches, RBC-EVs can be applied to enable the precise application in genetic diseases, inflammatory diseases, and cancer. Such innovations have the potential to overcome the clinical need and enable the biological complexity of mRNA- and CRISPR-Cas-based agents to provide a powerful delivery platform. Moreover, the review also demonstrates the unprecedented benefits of red blood cell EVs, which include immune evasion, scalability, and universal loading capacity, which can establish them as the next-generation delivery vehicles. Red blood cell EVs have the potential to increase the efficacy of precision medicine by increasing its feasibility. Lastly, we note the potential and translational issues in the provision of red blood cell EV-based mRNA and CRISPR-Cas therapeutic delivery of gene therapy.

Keywords:  CRISPR-Cas; delivery vehicles; mRNA therapeutics; red blood cell-derived extracellular vesicles; targeting strategy

DOI:  https://doi.org/10.2147/IJN.S579975
J Nanobiotechnology. 2026 Feb 26.

Engineering integrin αvβ8-targeted extracellular vesicles to deliver BDNF mRNA for motor recovery in spinal cord injury.

Ming-You Shie, Cheng-Di Chiu, Yeh Chen, Yen-Hong Lin, Min-Hua Yu, You-Pen Chiu, Po-Fan Chiu, Cheng-Yu Chen, Yi-Wen Chen, Mei-Chih Chen, Der-Yang Cho.

  Spinal cord injury (SCI) remains difficult to treat, and current interventions provide limited functional restoration and often require invasive procedures. Existing cell- or extracellular vesicles (EV)-based approaches are frequently administered alongside surgery, limiting therapeutic reach and overall efficacy. In this study, we developed an engineered extracellular vesicle (EV) platform by displaying a single-chain variable fragment (scFv) against integrin αvβ8 (αITGEV) and loading brain-derived neurotrophic factor mRNA (mBDNF). The construct maintained canonical EV identity and morphology, and showed predominant single particle co-positivity for targeting ligand and cargo. In neuron-microglia co-culture, mBDNF@αITGEV preferentially entered both cell types under injury-relevant stress, shifted microglia toward a repair-associated phenotype, reduced TNF-α and IL-1β, increased IL-4 and IL-10, and preserved neuronal architecture. Our results indicate that mBDNF@αITG-EVs significantly promote functional motor recovery by modulating the inflammatory microenvironment and inhibiting neuronal ferroptosis. Mechanistically, the delivery of BDNF mRNA bolstered GPX4 expression and stabilized mitochondrial dynamics, thereby mitigating secondary oxidative damage. This study provides a non-invasive strategy for precision nanomedicine in neuro-regeneration. Collectively, this study supports a non-invasive systemically administered, targeted EV-mRNA therapeutic strategy for spinal cord injury with translational potential.

Keywords:  BDNF mRNA; Extracellular vesicles; Integrin; Microglial polarization; Spinal cord injury

DOI:  https://doi.org/10.1186/s12951-026-04222-7
Front Pharmacol. 2026 ;17 1762630

Mesenchymal stem cell-derived exosomes in myocardial infarction repair: therapeutic potential and scaffold-based delivery strategies.

Vajiheh Azimian Zavareh, Negar Eslampoor, Sanaz Panahi-Alanagh, Latifeh Malekmohammad, Agata Stanek.

  Myocardial infarction (MI) remains a leading cause of global mortality, with current therapeutic modalities offering limited capacity for complete myocardial tissue regeneration. Advances in regenerative medicine have introduced stem cell-based approaches, among which mesenchymal stem cells (MSCs) have garnered significant scientific curiosity due to their multipotent differentiation potential and favorable safety profile. However, evidence suggests that the primary therapeutic effects of MSCs are mediated through their paracrine secretion of bioactive factors, notably exosomes. These MSC-derived exosomes (MSC-Exos) can modulate key aspects of cardiac repair, such as enhancing angiogenesis, preventing apoptosis, and alleviating inflammation by transferring genetic material such as miRNAs, proteins, and lipids and by activating molecular pathways critical to cardiac repair. Numerous studies as well as preclinical and clinical trials are currently investigating MSC-Exos for tissue regeneration. This review critically examines the biological characteristics and underlying mechanisms of MSC-Exos in myocardial repair, with particular focus on cell sources such as bone marrow-derived MSCs (BMMSCs), adipose-derived MSCs (ADSCs), and human umbilical cord MSCs (HUCMSCs), and evaluates their roles from multiple perspectives. Moreover, this review emphasizes innovative delivery approaches, including hydrogel-based systems, aimed at maximizing therapeutic effectiveness and accelerating translational potential. The integration of scaffold technologies and exosome engineering holds substantial promise for translating this cell-free approach into effective clinical treatments, presenting MSC-Exos as a transformative strategy with the potential to markedly improve outcomes in MI.

Keywords:  apoptosis; cardiac repair; exosome; inflammation; mesenchymal stem cells; myocardial infarction; scaffold

DOI:  https://doi.org/10.3389/fphar.2026.1762630
Sheng Wu Gong Cheng Xue Bao. 2025 Dec 08. pii: 1000-3061(2026)02-0797-14. [Epub ahead of print]42(2): 797-810

[Preparation of bacterial outer membrane vesicles modified with anti-angiogenic peptide AP25 on the surface and evaluation of their anti-tumor effects].

Shuo Zhao, Huilin Wang, Qing Wang, Xiaorui Li, Weihong Ren.

  Bacterial outer membrane vesicles (OMVs) have attracted widespread attention in the field of drug delivery due to their excellent biocompatibility, tumor penetration, and loading capacity. The anti-angiogenic peptide AP25 can block malignant tumor angiogenesis and has broad-spectrum anti-cancer activity. To achieve efficient delivery of AP25, we modified AP25 on the surface of OMVs through genetic engineering and explored their inhibitory effects on breast cancer and gastric cancer in vitro. The results indicated that the engineered OMVs had typical morphological characteristics of OMVs, and the particle size distribution conformed to the theoretical. Proteinase K digestion combined with Western blotting confirmed that AP25 was modified on the membrane surface of OMVs. Cell experiments showed that WAP25 OMVs significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 and HGC-27 cells, promoted the cell apoptosis, and downregulated the expression of tumor migration and angiogenesis-related proteins: integrin beta 1 (integrin β1), Homo sapiens inhibitor of DNA binding 1 (ID1), nuclear factor kappa-B (NF-κB), and vascular endothelial growth factor (VEGF). This study achieves effective delivery of protein drugs based on OMVs for the first time, providing new ideas for the anti-angiogenesis therapy for tumors and the functional development of bacterial OMVs.

Keywords:  angiogenesis inhibition; anti-angiogenic peptide AP25; antitumor; bacterial outer membrane vesicles (OMVs); drug delivery; engineering transformation

DOI:  https://doi.org/10.13345/j.cjb.250702
J Cosmet Dermatol. 2026 Mar;25(3): e70755

A Single-Center, Open-Label Study to Evaluate the Efficacy and Tolerability of Retinal Encapsulated in a Novel Biomimetic Exosome in the Treatment of Mild-To-Moderate Facial Photodamage.

Michael H Gold, Kaitlyn M Enright, Glynis Ablon, Sheila Barbarino, Suneel Chilukuri, Doris Day, David J Goldberg, Ted Lain, Ava Shamban, Todd Schlesinger.

   BACKGROUND: Numerous retinoid-based skincare products are available over-the-counter for photodamaged and photoaged skin, but are associated with objective (e.g., erythema, dryness, flaking, edema) and subjective (e.g., itching, tingling, stinging, burning) tolerability issues. A novel retinal formulation was developed using an engineered biomimetic vegan exosome as a delivery system. The formulation also contains proprietary and potent hyaluronic acid, as well as plant-based actives commonly used in traditional herbal medicines for their anti-inflammatory and antioxidant properties.
AIMS: Evaluate the efficacy and tolerability of this biomimetic exosome-encapsulated retinal product for treatment of mild-to-moderate facial photodamage.
PATIENTS/METHODS: Twenty females aged 35 to 65 years, with Fitzpatrick skin types I-VI, mild-to-moderate facial fine lines and wrinkles, and mild-to-moderate facial photodamage, were assessed at screening/baseline and weeks 2, 4, 8, and 12. Investigator- and participant-assessed evaluations were performed at each visit. The primary objective was to demonstrate a decrease in the appearance of fine lines and wrinkles, erythema, as well as a reduction of overall facial photodamage after a 12-week topical regimen. The secondary objective was to measure the frequency of adverse events throughout the study.
RESULTS: Statistically significant improvements in erythema, skin tone, skin texture, and lines/wrinkles were observed at all follow-up visits, compared to baseline. At weeks 8 and 12, all participants (100%) displayed improvements in facial aesthetics. Most participants (19/20; 95.00%) were satisfied with the product and would recommend it to others. No product-related adverse events were reported.
CONCLUSIONS: Daily use of this "hydrating retinal" improved signs of facial photodamage with none to mild signs of skin irritation.

Keywords:  anti‐aging; photo aging; retinol; skincare; tretinoin; vitamin A

DOI:  https://doi.org/10.1111/jocd.70755
Adv Sci (Weinh). 2026 Feb 27. e17554

Sirt3 Genetically Engineered Apoptotic Bodies Alleviate Skeletal Aging by Limiting Aggravated NLRP3 Inflammasome Activation of Senescent Macrophages.

Yanglin Wu, Shifeng Ling, Jiayi Mao, Hongyi Wang, Bo Wang, Zhenjia Che, Wenguo Cui, Ming Cai.

  Skeletal aging is characterized by increased fragility, reduced bone mass, and deterioration of bone microstructure. Although aging-related immune dysfunction of macrophages, namely immunosenescence, is known to contribute to this process, the underlying mechanism remains poorly understood. Here, we find that the senescence of macrophages leads to a decrease in the expression of Sirtuin3 (Sirt3), which in turn leads to increased basal and lipopolysaccharides (LPS)-induced protein expression of NLRP3 and facilitates the assembly of NLRP3 inflammasome in macrophages that mediates aging-related osteoporosis. Given the phagocytic property of macrophages, we develop a genetically engineered apoptotic body-based platform for targeted delivery of Sirt3 to macrophages and verify that Sirt3-enriched apoptotic bodies (ABs-Sirt3) delay skeletal aging by promoting ubiquitination and degradation of NLRP3. Our work reveals that Sirt3 plays a key role in regulating aggravated inflammatory responses that accelerate skeletal aging during macrophage senescence and illustrates a novel nanotechnology-based therapeutic approach targeting immune senescence-induced acceleration of skeletal aging, which may provide potential therapeutic value for human patients with age-related osteoporosis.

Keywords:  NLRP3 inflammasome; apoptotic body; macrophage; skeletal aging

DOI:  https://doi.org/10.1002/advs.202517554
Acta Biomater. 2026 Feb 23. pii: S1742-7061(26)00128-5. [Epub ahead of print]

Bioorthogonal and synthetic biology-engineered bacterial outer membrane vesicles for enhanced photo-immunotherapy.

Guannan Liu, Zhengyue Fei, Xinyue Tao, Huiqin Wang, Xueming Li, Hao Ren.

  Bacterial outer membrane vesicles (OMVs) have emerged as versatile platforms for cancer immunotherapy, yet their clinical translation is hindered by limited drug-loading capacity, suboptimal tumor accumulation, and rapid clearance, which collectively compromise the induction of robust antitumor immunity. Here, we engineer a multifunctional nanocarrier, OMV-mIL2-ICG-DBCO, that integrates cytokine delivery, photothermal therapy, and bioorthogonal targeting to overcome these obstacles. Using synthetic biology, parental bacteria are modified to autonomously produce interleukin-2 (mIL2)-enriched OMVs, thereby endowing the vesicles with intrinsic immunostimulatory activity. The photosensitizer indocyanine green (ICG) is subsequently encapsulated into OMVs via electroporation, enabling near-infrared light-triggered hyperthermia, immunogenic tumor cell death, and enhanced release of tumor-associated antigens. In parallel, metabolic glycoengineering with azide-functionalized sugar precursors induces N3 group expression on tumor cell surfaces, while OMVs are functionalized with dibenzocyclooctyne (DBCO), allowing highly specific bioorthogonal conjugation and selective vesicle accumulation within tumors. In vivo, OMV-mIL2-ICG-DBCO exhibits markedly improved tumor homing, potent photothermal ablation, and strong activation of antitumor immune responses, resulting in significant inhibition of primary tumor growth and reduced off-target toxicity compared with non-targeted controls. Collectively, this bioorthogonally targeted, photo-immunotherapeutic OMV platform provides an effective strategy to amplify antitumor immunity and represents a promising candidate for the treatment of breast cancer. STATEMENT OF SIGNIFICANCE: Bacterial outer membrane vesicles (OMVs) are promising bioinspired nanocarriers with inherent immunogenicity, but their therapeutic efficacy is limited by poor tumor targeting and low drug-loading capacity. Here, we develop a dual-engineered OMV platform that combines genetic IL-2 expression with bioorthogonal glycol-metabolic labeling (N3/DBCO) to achieve programmable immune modulation and tumor-specific delivery. The vesicles are further loaded with indocyanine green via electroporation, enabling photothermal-triggered immunogenic cell death that promotes antigen exposure and dendritic cell maturation. This synergistic integration of biological and chemical engineering endows OMVs with precise targeting, potent immune activation, and minimized off-target photothermal effects. The strategy introduces a biorthogonal targetable photo-immunotherapeutic nanoplatform, offering a versatile and generalizable framework for engineering living-derived biomaterials in cancer immunotherapy.

Keywords:  Bacterial outer membrane vesicles; Bioorthogonal; Immunotherapy; Interleukin-2; Photothermal therapy

DOI:  https://doi.org/10.1016/j.actbio.2026.02.044