bims-engexo 2026-08-16 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–08–16
eleven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

From Uptake to Therapeutic Function in Engineered Exosome Delivery Systems.
Engineered Brain-Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke.
Biomimetic exosomal delivery of ginsenoside Rd reduces post-stroke depression via microglial reprogramming in a pathway involving EGFR/JAK2/STAT3.
Exosome-based nanomedicine for neurological disorders: mechanisms, engineering, and therapeutic potential.
FGF21-modified adipose stem cell-derived exosomes promote wound healing by activating fibroblast glycolysis through AMPK/mTOR signaling.
Magnetically guided apoptotic mesenchymal stem cell-derived nanovesicles for the modulation of pathological remodeling in cardiac injury.
Long-Term Stabilization of Non-Bovine Milk Exosomes Using Lyophilization: Toward Oral Delivery of PROTAC Therapeutics.
MicroRNA-engineered extracellular vesicles for burn wound repair: burn-specific design and translational perspectives.
Camouflage Protein-Engineered Extracellular Vesicles Alleviate TMJ-OA by Hijacking Caspase-1 to Suppress Pyroptosis.
Modular engineered outer membrane vesicles for synergistic cancer immunotherapy via PD-L1 blockade and epigenetic reprogramming.
Reversing Antibiotic Resistance and Reprogramming Macrophage Polarization by Extracellular Vesicles from Fresh Schisandra chinensis: A Dual Pharmacological Strategy for Drug-Resistant Wound Infection and Sepsis.

Research (Wash D C). 2026 ;9 1389

From Uptake to Therapeutic Function in Engineered Exosome Delivery Systems.

Yiwei Li, Limin Jin, Pengli Gao, Mingmei Li, Zengkai Zhao, Jianjun Jiang, Ming An, Fangzhou Li.

Engineered exosomes are increasingly recognized as promising vehicles for precision drug delivery. Genetic display, chemical modification, physical loading, and hybrid vesicle construction have expanded their applications, while introducing additional variables to the interpretation of delivery outcomes. Because engineering can alter vesicle properties, receptor engagement, endocytic routing, intracellular trafficking, and functional readouts, tissue accumulation or cellular uptake alone is insufficient to define effective delivery. This review traces engineered exosome delivery from cellular uptake to therapeutic function, covering engineering strategies, targeting validation, endocytic routing, intracellular fate, and functional readouts. We further discuss the strengths and limitations of commonly used evaluation methods. Across biomedical applications, we emphasize that delivery evidence should be judged according to cargo type, site of action, disease model, and therapeutic mechanism. By linking engineering design, assay selection, and evidence strength, this review supports a more careful interpretation of engineered exosome delivery.

DOI: https://doi.org/10.34133/research.1389
Adv Sci (Weinh). 2026 Aug 11. e77064

Engineered Brain-Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke.

Bixin Shen, Chengxiang Zhang, Junhui Wang, Xichong Zhong, Shihao Chen, Xue Wang, Xiaokun Li, Li Lin.

  Diabetic stroke is characterized by a hyperglycemic and pro-inflammatory microenvironment that exacerbates neurovascular dysfunction. However, the blood-brain barrier (BBB) remains a formidable obstacle, restricting the delivery of most therapeutic molecules. To address this, we developed a non-invasive treatment strategy using engineered exosomes. Specifically, we fabricated FGF1-loaded exosomes functionalized with the rabies virus glycoprotein (RVG) peptide (FGF1-RVG Exo). This platform facilitates selective, neuron-targeted delivery of FGF1 to the ischemic penumbra via RVG-mediated transcytosis. In a diabetic stroke mouse model, FGF1-RVG Exo exhibited superior pharmacological efficacy compared to free FGF1, achieving robust therapeutic outcomes with only once-weekly administration. Notably, a single dose during the acute phase elicited a sustained hypoglycemic effect lasting up to two weeks and effectively ameliorated systemic insulin resistance. Locally, the accumulation of exosomes within the lesion led to a significant reduction in infarct volume and cell apoptosis, while promoting neovascularization and the recovery of motor and cognitive functions. This brain-targeted strategy achieves a peripheral-central synergistic modulation, addressing the multi-target requirements of diabetic stroke management. Collectively, our findings provide a novel paradigm for treating diabetic ischemic stroke and a potent strategy for the targeted delivery of growth factors to the central nervous system.

Keywords:  brain targeted drug delivery system; fibroblast growth factor; ischemic stroke; neural targeting; type 2 diabetes

DOI:  https://doi.org/10.1002/advs.77064
Pharmacol Res. 2026 Aug 08. pii: S1043-6618(26)00291-4. [Epub ahead of print]231 108376

Biomimetic exosomal delivery of ginsenoside Rd reduces post-stroke depression via microglial reprogramming in a pathway involving EGFR/JAK2/STAT3.

Jiaxin Chen, Xuanying Yin, Dong Yan, Qing Shi, Eyu Tan, Zhao Yan, Pengxiang Zhang, Wenjing Li, Meng Xiao, Qi Wang, Qiqi Fan, Pengfei Li, Jinman Liu.

  Post-stroke depression (PSD) represents a complex neuropsychiatric challenge characterized by persistent neuroinflammation and synaptic dysfunction, yet effective therapeutic interventions are constrained by the blood-brain barrier (BBB) and the lack of specific targets. Using a multidimensional screening strategy for Chaihu-Jia-Longgu-Muli Decoction (CLM), we identified ginsenoside Rd (Rd) as a key blood-absorbed bioactive constituent associated with Epidermal Growth Factor Receptor (EGFR) signaling. To overcome the bioavailability bottleneck, a biomimetic nanodelivery system is engineered by encapsulating Rd into microglia-derived exosomes (Exos@Rd). Based on the reported lesion-homing properties of microglia-derived exosomes, we developed a biomimetic Exos@Rd delivery system. Exosomal loading markedly enhanced the brain accumulation of Rd compared with free Rd. Mechanistically, it is demonstrated that aberrant EGFR activation functions as an upstream regulator of the JAK2/STAT3 cascade in microglia. Exos@Rd effectively suppressed this pathway and promoted anti-inflammatory microglial reprogramming, characterized by a shift from an M1-associated pro-inflammatory state toward an M2-associated anti-inflammatory profile. This microglia-centered anti-inflammatory regulation was accompanied by reduced oxidative stress and restoration of brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95) and Synapsin I (SYN1) expression. In a PSD mouse model, Exos@Rd significantly restores cerebral perfusion and alleviates depressive-like behaviors. Collectively, this study elucidates a novel EGFR-driven neuroinflammatory mechanism and presents a bio-inspired strategy for precision CNS drug delivery, offering a promising therapeutic paradigm for PSD.

Keywords:  Biomimetic delivery; EGFR signaling; Ginsenoside Rd; Immune microenvironment; Microglial exosomes; Post-stroke depression (PSD)

DOI:  https://doi.org/10.1016/j.phrs.2026.108376
Ther Deliv. 2026 Aug 11. 1-40

Exosome-based nanomedicine for neurological disorders: mechanisms, engineering, and therapeutic potential.

Nidhi Singh, Lahanya Guha, Alka Kumari.

  Exosomes are naturally occurring extracellular vesicles that have emerged as promising bio-inspired nanocarriers for the treatment of neurological disorders owing to their intrinsic biocompatibility, low immunogenicity, and ability to cross the blood-brain barrier. This review highlights recent advances in exosome biology, cargo-sorting mechanisms, and engineering strategies designed to enhance therapeutic delivery and targeting within the central nervous system. Particular emphasis is placed on the application of engineered exosomes in neurodegenerative diseases, stroke, spinal cord injury, neuropathic pain, and neuroinflammatory disorders. In addition, we discuss how exosomes compare with conventional delivery platforms and critically examine the major barriers limiting their clinical translation, including heterogeneity, scalability, reproducibility, purity, and regulatory standardization. By integrating mechanistic insights with translational perspectives, this review provides a framework for the rational design and future clinical implementation of exosome-based nanomedicines for neurological disorders. Relevant literature was identified through searches of PubMed, Scopus, Web of Science, and Google Scholar. Publications available from database inception through [Month Year] were screened using combinations of keywords including "exosomes," "extracellular vesicles," "neurological disorders," "brain-targeted delivery," "exosome engineering," "drug delivery," and "clinical trials." Additional relevant articles were identified through manual searches of reference lists from selected studies and recent reviews.

Keywords:  Exosomes; blood-brain barrier; drug delivery systems; exosomal engineering; neurological disorders

DOI:  https://doi.org/10.1080/20415990.2026.2715878
Cell Signal. 2026 Aug 04. pii: S0898-6568(26)00399-2. [Epub ahead of print]148 112742

FGF21-modified adipose stem cell-derived exosomes promote wound healing by activating fibroblast glycolysis through AMPK/mTOR signaling.

Kewei Chen, Xiaoyu Chen, Chenyi Wen, Wanying Chen, Zijin Liao, Yanming Chen, Liqun Li.

BACKGROUND: Chronic wound healing disorders remain a significant clinical challenge, largely due to the limited effectiveness of conventional therapeutic strategies. Emerging evidence suggests that engineered exosomes represent a promising cell-free therapeutic approach. This study aimed to elucidate the mechanisms by which fibroblast growth factor 21 (FGF21)-modified adipose-derived mesenchymal stem cell (ADSC) exosomes promote wound healing.
METHODS: ADSCs overexpressing FGF21 were established using genetic engineering, and FGF21-enriched exosomes (Exo@FGF21) were isolated and characterized using transmission electron microscopy and nanoparticle tracking analysis. The biological effects of Exo@FGF21 on human skin fibroblasts (HSFs) were assessed through proliferation, migration, invasion, and apoptosis assays. Glycolytic activity, glucose consumption, lactate production, ATP levels, and hydroxyproline content were evaluated to investigate metabolic changes. Mechanistic studies involved pharmacological inhibition of AMPK and knockdown of PFKFB3. Therapeutic efficacy was further examined in a mouse full-thickness skin defect model.
RESULTS: Exo@FGF21 exhibited typical exosomal morphology with diameters ranging from 80 to 150 nm and expressed canonical exosomal markers CD9 and CD63. In vitro, Exo@FGF21 significantly enhanced fibroblast proliferation, migration, and invasion, promoted collagen synthesis-related gene expression (COL1A1, COL3A1, FN1), and reduced apoptosis. Mechanistically, Exo@FGF21 activated AMPK, suppressed mTOR signaling, and upregulated PFKFB3 expression. Both AMPK inhibition and PFKFB3 knockdown markedly attenuated these pro-repair effects. Metabolic analyses demonstrated enhanced glycolysis, increased glucose utilization, elevated lactate production, and augmented ATP and hydroxyproline levels, indicating glycolytic metabolic reprogramming. In vivo, Exo@FGF21 accelerated wound closure, promoted epidermal regeneration, enhanced collagen deposition, and activated the AMPK/mTOR/PFKFB3 pathway.
CONCLUSION: FGF21-modified ADSC-derived exosomes promote wound healing by inducing fibroblast glycolytic metabolic reprogramming via the AMPK/mTOR/PFKFB3 signaling axis. These findings provide novel mechanistic insights and support the therapeutic potential of engineered exosome-based strategies for chronic wound repair.

DOI: https://doi.org/10.1016/j.cellsig.2026.112742
Acta Biomater. 2026 Aug 08. pii: S1742-7061(26)00536-2. [Epub ahead of print]

Magnetically guided apoptotic mesenchymal stem cell-derived nanovesicles for the modulation of pathological remodeling in cardiac injury.

Gyeongseo Yoo, Ji-Young Kang, Malgeum Park, Jaewoong Lee, Dasom Mun, Nuri Yun, Boyoung Joung.

  Inflammation and fibrosis can arise as consequences of cardiac injury and further contribute to the progression of heart failure (HF) and arrhythmias. Despite ongoing therapeutic advancements, effective treatments to modulate these pathological processes remain limited. To overcome these limitations, we developed a multifunctional nanotherapeutic system using apoptotic mesenchymal stem cell-derived nanovesicles (ANV) as biocompatible and immunomodulatory delivery platforms for small interfering RNA (siRNA) targeting the adipocyte enhancer binding protein 1 (AEBP1). ANV are constructed via an extrusion method and loaded with AEBP1-targeting siRNA (siAEBP1) through electroporation to form ANV-siAEBP1. The vesicles are then incubated with antibody-conjugated iron oxide magnetic nanoparticles (MNP), forming the ANVP-siAEBP1 complex. For targeted delivery to the injured myocardium, an anti-myosin light chain 3 (MLC3) antibody is incorporated, based on injury-associated MLC3 exposure for localized accumulation of ANVP-siAEBP1 at the injury site. Upon localization, intracellular release of siAEBP1 silences AEBP1 expression, downregulates pro-fibrotic signaling, and mitigates cardiac fibrosis. Simultaneously, the intrinsic anti-inflammatory effects of ANV prevent excessive inflammatory responses. This dual mechanism of action results in synergistic therapeutic effects, significantly attenuating both inflammation and fibrosis with enhanced targeting efficiency. Collectively, this engineered four-in-one nanovesicle platform offers a promising strategy for next-generation precision therapeutics in cardiac injury. STATEMENT OF SIGNIFICANCE: Cardiac injury often leads to heart failure, yet current therapies lack precise targeting and long-term effectiveness. Here, we develop a multifunctional nanocarrier system that enables targeted delivery of siRNA to injured cardiac tissue. This system combines nanoscale engineering with biological functionality, allowing gene regulation that reduces inflammation and fibrosis. By silencing adipocyte enhancer-binding protein 1 (AEBP1) via siRNA, our platform suppresses fibrosis and improves cardiac function in vivo, further supported by the inflammation-regulating properties of the nanovesicle. This work demonstrates how engineered biomaterials can be designed to control cellular responses and disease progression, offering a promising strategy for targeted gene therapy and cardiac repair.

Keywords:  Cardiac injury; Engineered apoptotic nanovesicles; Fibrosis; Gene silencing; Inflammation

DOI:  https://doi.org/10.1016/j.actbio.2026.08.013
J Drug Deliv Sci Technol. 2026 Jan;pii: 107821. [Epub ahead of print]115(Pt 2):

Long-Term Stabilization of Non-Bovine Milk Exosomes Using Lyophilization: Toward Oral Delivery of PROTAC Therapeutics.

Aakash Nathani, Sandeep Chary Padakanti, Arvind Bagde, Mandip Singh.

  The clinical translation of exosome-based therapeutics is limited by challenges in long-term storage, stability, and scalability. We developed and optimized a lyophilization protocol to stabilize camel and donkey milk-derived exosomes for oral delivery of ARV-110, a proteolysis-targeting chimera (PROTAC). Using 5% trehalose, 5% mannitol, and 2.5% glycine as cryoprotectants, lyophilization preserved exosome integrity, protein content, and expression of key markers (CD63, CD81, TSG101, Alix) during storage at -80°C. Reconstituted exosomes, maintained particle size and zeta potential comparable to fresh preparations. In vitro, ARV-110-loaded lyophilized exosomes showed enhanced cytotoxicity in LLC cells (p < 0.001) and increased transepithelial transport in MDCK assays (p < 0.05). In rats, ARV-110 delivered via lyophilized exosomes achieved a 1.77-fold higher Cmax and 1.73-fold higher AUC0-24 compared to free drug, with no change in Tmax. Lyophilized exosomes retained over 90% of protein content after 8 weeks at -80°C, whereas non-lyophilized controls retained <25%. These findings demonstrate that lyophilized milk exosomes are a scalable, biocompatible platform for oral delivery of poorly bioavailable therapeutics like PROTACs, addressing major formulation and stability challenges and supporting their translational potential in drug delivery.

Keywords:  ARV-110-PROTAC; Donkey and Camel milk; Long-term stability; Lyophilization; Non-bovine Milk Exosomes; Oral drug delivery

DOI:  https://doi.org/10.1016/j.jddst.2025.107821
J Burn Care Res. 2026 Aug 13. pii: irag133. [Epub ahead of print]

MicroRNA-engineered extracellular vesicles for burn wound repair: burn-specific design and translational perspectives.

Xinrui Jin, Jing Wang.

  Burn wound healing remains a major clinical challenge. Mesenchymal stem cell-derived extracellular vesicles engineered to deliver defined microRNA cargo or modulate endogenous microRNA profiles have emerged as promising cell-free therapeutics, but native extracellular vesicle preparations remain constrained by low yield, heterogeneity, insufficient targeting, and incomplete cargo control. Moreover, much of the current evidence still comes from non-burn wound models. This review presents a burn-oriented framework that aligns upstream parental-cell programming, downstream vesicle modification, and biomaterial-assisted delivery with key burn-specific barriers, including burn depth, eschar, infection, hypoxia, systemic inflammation, inhalation injury, grafting requirements, and temporal immune dysregulation across the systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition. We also discuss translational requirements that are often underemphasized in general wound-healing reviews, including dose scaling for large total body surface area burns, repeat application, compatibility with debridement and grafting, storage and thawing in burn centers, sterility, use in infected wounds, and whether local extracellular vesicle delivery can mitigate systemic dysfunction. Overall, microRNA-engineered extracellular vesicles are a versatile platform for burn wound repair; however, clinical translation remains speculative without large-animal, infected-burn, grafting, long-term scar, and human safety data.

Keywords:  biomaterial-assisted delivery; burn wound healing; mesenchymal stem cells; microRNA-engineered extracellular vesicles; translational medicine

DOI:  https://doi.org/10.1093/jbcr/irag133
J Extracell Vesicles. 2026 Aug;15(8): e70342

Camouflage Protein-Engineered Extracellular Vesicles Alleviate TMJ-OA by Hijacking Caspase-1 to Suppress Pyroptosis.

Yufei Liu, Jie Zhou, Yukang Wang, Zhihui Hu, Guimin Yin, Mengsen Zhu, Jianke Huo, Chenyang Zhang, Yiming Wang, Shuang Fu, Jinpeng Wan, Jie Wang, Lanju Xu, Zhiling Zhang, Shufang Wang.

  Temporomandibular joint osteoarthritis (TMJ-OA) is highly prevalent with an insidious onset. Severe inflammation and significant degenerative changes are often associated with the condition, and current clinical treatments remain inadequate. In this study, we focus on pyroptosis and engineered the camouflage protein (GSDMD-C) attached to the membrane surface of small extracellular vesicles (sEVs)-sEV-p. sEV-p has two key effects: firstly, the inherent immunomodulatory and nutritional support properties of sEVs promote the recovery of cellular function under pathological conditions; secondly, camouflage protein bind to the activated caspase-1, reducing the cleavage of endogenous GSDMD. The therapeutic effects of sEV-p were evaluated through in vitro experiments and treatment of TMJ-OA models in mice and Bama pigs. We further elucidated the mechanisms by single-cell RNA sequencing analysis. Results show that sEV-p alleviates the abnormal activation of inflammatory factors induced by pyroptosis, accompanied by a reduction in the proportion of inflammatory cells and a mitigation of acute inflammatory responses.

Keywords:  gasdermin D; pyroptosis; small extracellular vesicles; temporomandibular joint osteoarthritis; tissue regeneration

DOI:  https://doi.org/10.1002/jev2.70342
Front Immunol. 2026 ;17 1915499

Modular engineered outer membrane vesicles for synergistic cancer immunotherapy via PD-L1 blockade and epigenetic reprogramming.

Longxue Guan, Qinxiao Sun, Dandan Liang, Zhimin Li, Shiqi Zhang, Laili Huang, Xingang Guan, Hongxia Feng.

  Immune checkpoint inhibitors have significantly improved therapeutic outcomes in advanced melanoma; however, their clinical efficacy is greatly limited by low overall response rates and the primary or acquired resistance. Here, we developed a SpyCatcher-engineered bacterial outer membrane vesicle (OMV) platform for the co-delivery of a PD-1/PD-L1 inhibitor, the D-PPA1 peptide, and the epigenetic regulator zebularine (Zeb). The resulting co-delivery system, OMV@PPA/Zeb, effectively blocked PD-1/PD-L1 interactions and markedly upregulated melanoma-associated antigens, including CD146 and TRP1, in melanoma cells. In a subcutaneous melanoma mouse model, OMV@PPA/Zeb substantially suppressed tumor growth without noticeable systemic toxicity. Moreover, OMV@PPA/Zeb significantly promoted the infiltration and activation of CD8+ T cells while reducing regulatory T cells (Tregs) within the tumor microenvironment. The potent antitumor immune response elicited by this platform contributed to its enhanced therapeutic efficacy against melanoma. Overall, this study provides a modular OMV-based strategy for combination immunotherapy in advanced tumors.

Keywords:  OMVs; PD-L1 blockade; SpyCatcher/SpyTag; cancer immunotherapy; epigenetic regulation

DOI:  https://doi.org/10.3389/fimmu.2026.1915499
Pharmacol Res. 2026 Aug 14. pii: S1043-6618(26)00314-2. [Epub ahead of print] 108399

Reversing Antibiotic Resistance and Reprogramming Macrophage Polarization by Extracellular Vesicles from Fresh Schisandra chinensis: A Dual Pharmacological Strategy for Drug-Resistant Wound Infection and Sepsis.

Heng Wang, Yuming Liu, Jian Zhang, Jianfeng Wang.

  The rapid global escalation of multi-drug resistant (MDR) infections, ranging from localized chronic MRSA-infected wounds to systemic CRE-induced sepsis, has necessitated the urgent development of innovative antimicrobial potentiators. Herein, we identify Schisandra chinensis-derived extracellular vesicles (SCEVs) as a versatile, biogenic nanoplatform capable of simultaneously reversing bacterial resistance and resolving pathological inflammation. SCEVs exhibit intrinsic, broad-spectrum antibacterial activity and function as potent antibiotic sensitizers. At a low dose, SCEVs reduced the MICs of clinical MDR strains by up to 20-fold, achieving a fractional inhibitory concentration index (FICI) of 0.215. Leveraging this synergy, we engineered meropenem-loaded SCEVs (Mero@SCEVs) to achieve targeted intracellular delivery with an encapsulation efficiency of 20%. Integrated proteomic analyses unveiled that SCEVs exert their multifaceted efficacy through a dual-action mechanism whereby chitinase and Histone H4 disrupt bacterial membrane integrity, while ATP synthase targets F-type ATPase to deplete intracellular energy levels in pathogens. Simultaneously, SCEVs exert profound immunomodulatory effects by scavenging 71.4% of excessive ROS and driving macrophage polarization from a pro-inflammatory M1 phenotype to a pro-healing M2 phenotype. To facilitate clinical translation, a ROS-responsive PBA-HAMA/PVA hydrogel was developed for the sustained delivery of SCEVs to diabetic wounds, accelerating closure within 15 days. Beyond topical therapy, intraperitoneal injection of SCEVs rescued 60% of mice from lethal CRE-induced sepsis by suppressing cytokine storms and alleviating multi-organ damage. Collectively, this work establishes SCEVs as a novel antibiotic adjuvant strategy with dual antimicrobial and immunomodulatory pharmacology for managing the drug-resistant bacterial infectious continuum from localized wounds to systemic sepsis.

Keywords:  Antimicrobial resistance; Cross-kingdom regulation; Immunomodulation; Plant-derived extracellular vesicles; Schisandra chinensis

DOI:  https://doi.org/10.1016/j.phrs.2026.108399