bims-engexo Biomed News
on Engineered exosomes
Issue of 2026–08–09
eleven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.
  2. Engineered Extracellular Vesicles As a New Delivery Platform for Migraine.
  3. Thermally Induced Reassembly of Ginger Extracellular Vesicles for Oral Therapy of Intestinal Inflammation.
  4. Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.
  5. Exosome-Inspired Nanocarriers in Cancer Therapy: Bio-Derived Nanotechnology Meets Nano Drug Delivery.
  6. Bacterial extracellular vesicles: mechanisms, engineering strategies, and therapeutic potential for inflammatory bowel disease.
  7. Redirecting Monocyte Differentiation With Engineered Extracellular Vesicles for Glioma Immunotherapy.
  8. Advances in Exosome-Based Therapy for Cardiovascular Disease: Traditional Chinese Medicine Offering New Avenues for Exosome Functionalization.
  9. Ginger-derived exosome-like nanoparticles incorporated into hydrogel matrix for enhanced oral delivery of celastrol to alleviate ulcerative colitis.
  10. EV-LYSG101: Extracellular Vesicles Loaded With Lysin LYSG101 for Potent Anti-Staphylococcal Activity.
  11. Mitochondria-enriched BMSC exosomes restore microglia-neuron cross-talk in Parkinson's disease via PINK1/parkin and PI3K/Akt/mTOR pathways.
  1. Daru. 2026 Aug 03. pii: 55. [Epub ahead of print]34(2):
    Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.
    Amr Ali Mohamed Abdelgawwad El-Sehrawy, Hassan Youssef Hussein, Ozodbek Nematov, Mirza R Baig, Dhara N Patel, Priya Priyadarshini Nayak, Safa Alkayyat, Neeraj Bainsal, Gunjan Singh, Tina Saeed Basunduwah.
      Exosome-mediated delivery of small interfering RNA (siRNA) has emerged as a promising therapeutic strategy for cancer treatment, offering precise gene silencing with minimal off-target effects. Exosomes, naturally secreted extracellular vesicles, provide biocompatible carriers that protect siRNA from enzymatic degradation and facilitate efficient uptake by tumor cells. Their natural tropism, driven by surface proteins such as integrins and tetraspanins, promotes cellular adhesion and interactions within the tumor microenvironment, facilitating the delivery of therapeutic cargo. Preclinical studies have demonstrated that exosome-delivered siRNAs can suppress oncogenes, inhibit tumor growth, reverse chemoresistance, and modulate immune responses by targeting stromal and immune components. Engineering approaches, including surface functionalization and hybrid exosome-nanoparticle systems, further enhance stability, payload capacity, and tumor-homing efficiency. Combination strategies with chemotherapy, immunotherapy, or phototherapy have shown synergistic effects, allowing simultaneous inhibition of survival pathways, promotion of apoptosis, and remodeling of the immunosuppressive microenvironment. Early-phase clinical studies indicate safety, effective biodistribution, and functional gene silencing, highlighting the translational potential of exosome-mediated siRNA therapeutics. Challenges such as scalable production, cargo heterogeneity, and regulatory considerations remain, but ongoing advances in exosome engineering and patient-derived vesicles are poised to overcome these barriers. This review aims to comprehensively summarize the current state, therapeutic applications, and translational prospects of exosome-mediated siRNA delivery in cancer.
    Keywords:  Cancer treatment; Drug resistance; Exosomes; Gene silencing; Tumor microenvironment; siRNA therapy
    DOI:  https://doi.org/10.1007/s40199-026-00631-z
  2. ACS Appl Bio Mater. 2026 Aug 03. 9(15): 6792-6820
    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
  3. Research (Wash D C). 2026 ;9 1377
    Thermally Induced Reassembly of Ginger Extracellular Vesicles for Oral Therapy of Intestinal Inflammation.
    Linhai Hou, Jie Cao, Shengjie Gao, Xiaofan Wang, Zhongxian Zhang, Meiqi Li, Yu Mao, Changhong Liu, Ling Yan, Haiping Hao, Lei Zheng.
      Plant-derived extracellular vesicles are promising candidates for oral drug delivery, yet their clinical translation is hindered by limited targeting precision and inconsistent systemic absorption. While surface engineering can enhance tissue accumulation, strategies that preserve biocompatibility and enable scalable production remain limited. Here, we introduce boiling as a simple thermal processing approach that structurally reconfigures ginger extracellular vesicles (GEVs) into functionally enhanced, thermally reassembled GEVs (T-GEVs). The surface architecture of T-GEVs is enriched with key vesicle trafficking regulators, including V-type proton adenosine triphosphatase subunit G, ARF1, and β-adaptin-like protein. This specific composition drives their tissue-specific accumulation in the intestine and liver and potentiates clathrin-dependent cellular uptake in intestinal cells by 8.57-fold. Beyond superior intrinsic anti-inflammatory activity through NLRP3 inflammasome suppression, T-GEVs function as an efficient oral delivery platform. When loaded with tumor necrosis factor-α (TNF-α) small interfering RNA, they enable a synergistic therapy that combines innate anti-inflammatory activity with targeted gene silencing of TNF-α, showing potent efficacy in colitis. Our findings position boiling as a natural strategy for enhancing the bioactivity and targeted oral delivery potential of GEVs.
    DOI:  https://doi.org/10.34133/research.1377
  4. Precis Clin Med. 2026 Sep;9(3): pbag019
    Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.
    Huiqin Bian, William Tse, Gang Huang, Shujun Liu.
      mRNA therapeutics are transitioning from transient anti-viral vaccines into precise cancer immunotherapies capable of orchestrating potent antigen-specific T-cell and humoral responses. However, therapeutic resistance within immunologically "cold" tumors remains a formidable barrier, necessitating multiaxial optimization across transcript architecture, neoantigen selection, delivery vector engineering, and tumor microenvironment (TME) reprogramming. This review synthesizes critical breakthroughs in mRNA biochemistry-including chemical nucleotide modifications, optimized untranslated regions, structural codon adjustments, and stringent purification methodologies-that extend transcript longevity while limiting off-target reactogenicity to maximize functional antigen expression. We evaluate multiomic neoantigen discovery workflows leveraging genomics, transcriptomics, immunoproteomics, and computational HLA-binding algorithms to refine patient-specific target selection. Next, we dissect advanced lipid nanoparticles, surface-functionalized biomaterials, and engineered extracellular vesicles optimized to enhance antigen-presenting cell tropism and lymphoid homing. We further detail how vaccine-induced cytokine fluxes actively remodel the TME, successfully reversing local immune tolerance and driving robust effector leukocyte infiltration into the tumor stroma. Specifically, we highlight the convergence of mRNA-mediated cytokine signaling and epigenetic imprinting, which cooperatively induce trained immunity for durable preventive surveillance. Finally, we delineate rational combinations with immune checkpoint blockades while addressing translational challenges: identifying predictive biomarkers, mapping presentation kinetics, and structuring adaptive clinical trial frameworks.
    Keywords:  epigenetic reprogramming; exosome-mediated delivery; multivalent mRNA vaccines; precision immunotherapy; trained immunity; tumor microenvironment plasticity
    DOI:  https://doi.org/10.1093/pcmedi/pbag019
  5. Int J Nanomedicine. 2026 ;21 613224
    Exosome-Inspired Nanocarriers in Cancer Therapy: Bio-Derived Nanotechnology Meets Nano Drug Delivery.
    Bingya Zhang, Yihang Gao.
      Traditional cancer therapy has limitations due to a lack of specificity and efficiency in tumor-targeting, toxicity issues, and biological barriers, which affect the clinical efficacy of traditional agents as well as synthetically designed carriers. Exosomes have gained popularity as excellent biological carriers owing to their inherent biocompatibility, capability to overcome biological barriers, and ability to transport cargoes between cells naturally. This review discusses how engineering of exosomes, hybrid exosomes, and exosome mimics could be employed to deliver therapies, enhance tumor penetration, and enable multimodal treatment of cancers, including chemotherapy, gene therapy, immunotherapy, and theranostics. The biomimetic and hybrid platforms may overcome key limitations of native exosomes, particularly low production yield, heterogeneity, limited drug-loading efficiency, and scalability constraints, while preserving desirable biological functionality. Moreover, the review also emphasizes that the standardization in manufacturing, reproducibility in cargo, safety evaluation, and regulatory approval are the major obstacles to clinical application. Unlike many earlier reviews that were mainly centered on native exosomes, the current review discusses the engineering aspects of exosome-like nanoplatforms from a translational viewpoint.
    Keywords:  bio-derived drug delivery; cancer therapy; exosomes; extracellular vesicles; tumour microenvironment
    DOI:  https://doi.org/10.2147/IJN.S613224
  6. Nanomedicine (Lond). 2026 Aug 06. 1-13
    Bacterial extracellular vesicles: mechanisms, engineering strategies, and therapeutic potential for inflammatory bowel disease.
    Qing Ji, Huabiao Chen, Xiaochun Sun.
      Clinical management of inflammatory bowel disease (IBD) is hampered by limited therapeutic targets, primary non-response, secondary loss of efficacy, and safety risks, which undermine clinical outcomes. Probiotics and postbiotics represent promising preclinical candidates to alleviate these unmet clinical bottlenecks. Bacterial extracellular vesicles (BEVs) are naturally secreted bacterial nanovesicles carrying abundant bioactive cargos, whose bioactivity and safety are highly strain-dependent. Probiotics-derived BEVs can remodel gut homeostasis, repair epithelial barriers, and regulate mucosal immunity to suppress the inflammatory vicious cycle in IBD, while pathogen-/pathobiont-derived BEVs loaded with lipopolysaccharide and virulence factors exacerbate intestinal inflammation. Native BEVs are restricted by low cargo loading, poor gastrointestinal stability and inadequate colon tropism. Rational engineering strategies, including surface modification, self-loading hybridization, genetic manipulation, and pH-responsive coating, can optimize the therapeutic performance of BEVs. This review systematically summarizes BEVs biological mechanisms, engineering approaches, and translational obstacles and outlines prospects for the design of intelligent multifunctional BEVs and standardized large-scale manufacturing as future directions, providing theoretical support for oral BEVs nanotherapies against IBD.
    Keywords:  Inflammatory bowel disease; bacterial extracellular vesicles; bioactive cargos; engineering strategies; probiotics
    DOI:  https://doi.org/10.1080/17435889.2026.2713674
  7. Adv Sci (Weinh). 2026 Aug 05. e76910
    Redirecting Monocyte Differentiation With Engineered Extracellular Vesicles for Glioma Immunotherapy.
    Yuanwei Pan, Xuan Liu, Qian-Fang Meng, Lei Cao, Rongrong Li, Yangtao Xu, Jing Zhang, Chenchen Zhao, Lang Rao, Chen Yu.
      During glioma progression, monocytes abundantly infiltrate but primarily differentiate into immunosuppressive macrophages to promote tumor growth. Redirecting monocyte differentiation offers a compelling yet underexplored therapeutic opportunity. In this work, we found M1-polarized macrophage-derived extracellular vesicles (M1-EVs) efficiently induced monocytes to differentiate into anti-tumor macrophages via tumor necrosis factor alpha (TNF-α)-mediated signaling. Despite promising, the therapeutic efficacy of M1-EVs was constrained by insufficient glioma accumulation and CD47-mediated phagocytic inhibition. To address this challenge, we further engineered M1-EVs with dual-targeting specificity by genetically incorporating a tumor-directed chimeric antigen receptor (CAR) against IL13Rα2 or EGFRvIII together with CD47-blocking SIRPα variants. The resulting dual-targeting EVs (M1-CS-EVs) exhibited enhanced blood-brain barrier (BBB) penetration and glioma accumulation while locally disrupting CD47-SIRPα interactions. In three orthotopic glioma models, M1-CS-EVs elicited a potent anti-tumor immune response and enhanced tumor phagocytosis, significantly suppressing tumor growth while prolonging animal survival. Our findings establish a platform technology for directing monocyte differentiation toward anti-tumor phenotypes, offering a broadly applicable strategy for glioma treatment.
    Keywords:  cancer immunotherapy; dual targeting; extracellular vesicles; glioma; monocyte‐derived macrophage
    DOI:  https://doi.org/10.1002/advs.76910
  8. Phytochem Anal. 2026 Aug 02.
    Advances in Exosome-Based Therapy for Cardiovascular Disease: Traditional Chinese Medicine Offering New Avenues for Exosome Functionalization.
    Yi Chen, Xiaoyu Sun, Yingbo Ouyang, Rong Miao, Atinga Vallada, Rui Liu, Jingwen Guo, Chuwen Wang, Shiqi Zhang, Lin Li, Zhe Gao, Qilong Wang, Han Zhang, Ling Leng.
       BACKGROUND: Cardiovascular diseases (CVDs) remain a leading cause of global mortality and impose a substantial health and economic burden worldwide. Exosomes, as promising endogenous nanocarriers, have emerged as a powerful tool for the prevention and treatment of CVDs. In particular, advanced functionalization strategies have largely enhanced exosomal therapeutic efficacy in vivo. Notably, Traditional Chinese Medicine (TCM) and its bioactive components exert profound regulatory effects on exosomes.
    METHODS: In this review, we systematically summarize exosome-based therapeutic strategies for CVDs, along with state-of-art functionalization approaches to optimize exosomal cargo loading and targeted delivery. We further provide a comprehensive overview of TCM-mediated exosomal regulation.
    RESULTS: We found that TCM and TCM-derived chemicals can optimize exosomal cargo loading, especially the loading of microRNAs (miRNAs) and bioactive chemicals. More importantly, TCM and chemicals can promote exosomal secretion, which provides new avenues for exosomal-scale production. Besides, there are synergistic effects between exosomes and TCM when co-administered.
    CONCLUSION: Collectively, exosome-based systems hold great promise for CVD therapy, and TCM provides novel strategies for exosomal functionalization, which substantially enhances exosomal-mediated therapeutic efficacy for CVDs.
    Keywords:  Traditional Chinese Medicine; cardiovascular disease; exosomes; functionalization; herbs; secretion
    DOI:  https://doi.org/10.1002/pca.70085
  9. Int J Pharm. 2026 Aug 07. pii: S0378-5173(26)00704-0. [Epub ahead of print] 127256
    Ginger-derived exosome-like nanoparticles incorporated into hydrogel matrix for enhanced oral delivery of celastrol to alleviate ulcerative colitis.
    Nuannuan Li, Ye Jin, Yating Zhao, Bo Li, Wenjun Yu, Xinfeng Liu, Jinguang Liu, Yuanlei Fu.
      Celastrol (Cel), a highly promising natural product isolated from traditional Chinese medicine, exhibits potent therapeutic efficacy against ulcerative colitis (UC). Nevertheless, its poor colon-targeting efficiency, insufficient capacity to penetrate the intestinal mucus layer, and low cellular internalization significantly compromise therapeutic outcomes in UC treatment. To address these critical limitations, herein we rationally designed a exosome-hydrogel hybrid system (Cel-GDNPs@Gel) by first encapsulating Cel into ginger-derived exosome-like nanoparticles (GDNPs), which were subsequently dispersed within a glycyrrhizic acid (GA) hydrogel matrix. Experimental studies confirmed that GDNPs were successfully isolated and characterized with uniform size distribution and round- or cup-shaped morphology, and Cel was successful encapsulated into GDNPs. The GA hydrogel endowed the system with excellent pH-sensitivity and robust mucoadhesive properties, thereby facilitating enhanced accumulation and prolonged retention at the colon site. Moreover, GDNPs promoted efficient mucus penetration and cellular uptake of Cel. Notably, both GDNPs and GA could exert synergistic therapeutic effects with Cel. Accordingly, in vitro and in vivo studies demonstrated that Cel-GDNPs@Gel significantly alleviated colitis symptoms, suppressed the expression of pro-inflammatory cytokines, attenuated oxidative stress, regulated macrophage polarization, promoted intestinal mucosal barrier repair, and restored intestinal homeostasis. Furthermore, this delivery system exhibited favorable biosafety with no obvious systemic toxicity. Collectively, this multifunctional Cel-GDNPs@Gel platform offers a safe and effective strategy for the oral treatment of UC.
    Keywords:  Anti-inflammation; Antioxidant; Ginger-derived exosome-like nanoparticles; Intestinal injury repair; Macrophage polarization; Microbiota regulation
    DOI:  https://doi.org/10.1016/j.ijpharm.2026.127256
  10. J Extracell Biol. 2026 Aug;5(8): e70174
    EV-LYSG101: Extracellular Vesicles Loaded With Lysin LYSG101 for Potent Anti-Staphylococcal Activity.
    Dominique B Hoelzinger, Ava M Koehler de Celaya, Cheryl E Myers, Natasha P Dyal, Christopher F Saling, Raymond Schuch, Gina A Suh.
      Biofilm-associated staphylococcal infections remain exceptionally difficult to treat due to the presence of resilient staphylococcal biofilms and the limited effectiveness of currently available antibiotics. To combat persistent infections, providers are often forced to use prolonged courses of combination antimicrobial therapies that have significant toxicities with limited effectiveness, leading to increased hospital stays, substantial health care costs and a rise in patient morbidity and mortality. Staphylococcus aureus is a dominant cause of recalcitrant biofilms, for which novel non-antibiotic therapeutics are critically needed. Lysins, a class of protein-based antimicrobials, rapidly kill staphylococci, exhibit potent anti-biofilm activity, have a low propensity of resistance development and synergy with antibiotics. To address this unmet need, we evaluate an extracellular vesicle (EV)-based delivery platform for the engineered anti-staphylococcal lysin LYSG101, designed to improve stability and localization at sites of infection. Initial proof-of-concept work is provided here, demonstrating that human serum-derived EVs can be loaded with LYSG101 to exert a potent in vitro antimicrobial effect against both planktonic and biofilm forms of S. aureus. EV-mediated delivery achieved activity equivalent to free lysin, with additional translational advantages including stability and the potential for sustained intra-articular retention. This work supports further development of the EV-mediated lysin delivery as a broadly applicable antimicrobial platform, with potential future applications in biofilm-associated infections, including prosthetic joint infection (PJI).
    Keywords:  LYSG101; MRSA; Staphylococcus aureus; antimicrobial; extracellular vesicles; lysin; prosthetic joint infection
    DOI:  https://doi.org/10.1002/jex2.70174
  11. Brain Res. 2026 Aug 05. pii: S0006-8993(26)00349-5. [Epub ahead of print] 150487
    Mitochondria-enriched BMSC exosomes restore microglia-neuron cross-talk in Parkinson's disease via PINK1/parkin and PI3K/Akt/mTOR pathways.
    Shanshan Shi, Ruyue Liu, Chang Liu, Yuyao Chen, Yujun Pan, Chunyan Wang.
       BACKGROUND: Mitochondrial dysfunction and neuroinflammation drive dopaminergic neuron loss in Parkinson's disease (PD). While BMSC-derived small extracellular vesicles (BMSC-Exo) are neuroprotective, their ability to repair mitochondrial deficits is limited. We engineered mitochondrial-enriched sEVs (Exo-Mito) to evaluate their effects on microglia-neuron interactions in a PD-relevant model.
    METHODS: BMSC-Exo-Mito were characterized via TEM, NTA, and immunoblotting. Their therapeutic efficacy was assessed using an MPP + -induced BV2/SH-SY5Y transwell co-culture model. Assessments included ROS levels, mitochondrial membrane potential, ATP quantification, mitophagy flux, and signaling pathway analysis.
    RESULTS: Exo-Mito significantly restored mitochondrial homeostasis by reducing ROS, preserving membrane potential, and increasing ATP production. Mechanistically, Exo-Mito enhanced PINK1/Parkin-dependent mitophagy and PGC-1alpha/TFAM-mediated biogenesis. In BV2 microglia, Exo-Mito suppressed the NF-kappaB/NLRP3 axis, reduced proinflammatory cytokines, and promoted M2 polarization. In SH-SY5Y cells with dopaminergic phenotype, Exo-Mito was associated with reactivated PI3K/Akt/mTOR signaling, preserved tyrosine hydroxylase expression, and inhibited apoptosis. Functionally, Exo-Mito improved SH-SY5Y cell and restored microglial migratory capacity, showing superior efficacy to unmodified BMSC-Exo.
    CONCLUSION: Mitochondria-enriched BMSC sEVs protect SH-SY5Y cells by coordinating mitochondrial quality control and modulating neuroinflammation. These findings support Exo-Mito as a promising cell-free therapeutic strategy for Parkinson's disease.
    Keywords:  Mesenchymal stem cells; Mitochondria; Mitophagy; Neuroinflammation; PI3K/Akt/mTOR; Parkinson’s disease; Small extracellular vesicles
    DOI:  https://doi.org/10.1016/j.brainres.2026.150487
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