Journal of Extracellular Vesicles最新文献

{"title":"Dual-Targeted M1 Macrophage Extracellular Vesicles Reprogram the Tumor Microenvironment and Enhance Natural Killer Cell Immunotherapy in Breast Cancer","authors":"Su Jin Kang,&nbsp;Gichan Baek,&nbsp;Suwun Ju,&nbsp;Gunhee Kim,&nbsp;Seongjin Gwak,&nbsp;Won Jong Rhee","doi":"10.1002/jev2.70379","DOIUrl":"10.1002/jev2.70379","url":null,"abstract":"<p>Breast cancer is the most commonly diagnosed cancer worldwide and a leading cause of cancer-related mortality in women. Despite therapeutic advances, treating advanced or recurrent cases is substantially hampered by drug resistance and the immunosuppressive tumor microenvironment (TME). Here, we report a breakthrough immunotherapeutic strategy using dual-targeted extracellular vesicles from pro-inflammatory M1 macrophages, hyaluronic acid (HA), and cyclic RGD (M1EV_HA/cRGD), which function as molecular bridges to physically link natural killer (NK) cells with cancer cells. Our platform simultaneously reprograms the hostile TME while activating potent antitumor immunity. HA is incorporated to engage CD44 receptors on NK cells and cRGD peptides to bind tumor-overexpressing integrins, establishing precision dual-targeting. M1EV_HA/cRGD could physically tether NK cells directly to tumors, and deliver inflammatory cytokines and miRNAs that transform the immunosuppressive TME into a pro-inflammatory battlefield, substantially amplifying immune activation. <i>In vitro</i> and <i>in vivo</i> studies demonstrate that M1EV_HA/cRGD significantly enhances NK cell clustering at tumor sites, activation status, and cytotoxic killing of breast cancer cells. Unlike single-targeted approaches, this dual-targeting mechanism achieves simultaneous TME reprogramming and enhanced immune-tumor engagement. M1EV_HA/cRGD is a paradigm shift in solid tumor immunotherapy that directly addresses breast cancer treatment failure, can overcome therapeutic resistance, and substantially improve patient survival outcomes.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved and Tissue-Specific RNA and Protein Cargos of Small Extracellular Vesicles From 120 Tissue Sites Across 34 Organs in a Single Pig","authors":"Naixiang Yu,&nbsp;Jinxiu Liu,&nbsp;Chenliang Lai,&nbsp;Siyi Liu,&nbsp;Jiacheng Wei,&nbsp;Jiahong Zhong,&nbsp;Sanya Xiong,&nbsp;Qingjie Zeng,&nbsp;Junwu Ma,&nbsp;Zhou Zhang,&nbsp;Zhiyan Zhang","doi":"10.1002/jev2.70374","DOIUrl":"10.1002/jev2.70374","url":null,"abstract":"<p>Small extracellular vesicles (sEVs) carry diverse cargo essential for intercellular communication, but their organism-wide characterization across all tissues is still limited. Here, we present a multi-omics sEV atlas covering the whole-body of 120 tissue sites, four body fluids and nine gastrointestinal contents from the same pig. We identified 7995 proteins, 337 miRNAs as well as 105,409 transcripts (93,409 full-length) in sEVs by mass spectrometry, next- and third-generation RNA sequencing. Among these, a conserved cargo set of 252 proteins, 18 miRNAs and 1227 transcripts was defined, including RNA-binding proteins (ANXA2, ALIX and MVP), mitochondrial proteins (ATP5F1A, COX6C and VDACs), the let-7 miRNA family and ferritin genes (<i>FTH1</i>/<i>FTL</i>). Notably, sEV biogenesis-associated ACTG1, CFL1 and ANXA2 were detected in all samples, suggesting their potential as novel sEV protein markers. In contrast, 2638 proteins, 152 miRNAs and 1000 transcripts showed organ-specific expression patterns, which are likely to underpin organ-specific biological processes. Moreover, by using this multi-omic dataset and additional RIP assays, we found that HNRNPU participates in the sorting of hypoxia-responsive <i>EPAS1</i> into sEVs. This comprehensive sEV atlas establishes a foundation for future studies in sEV cell biology.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shear Stress-Stimulated Trafficking of Endothelial Piezo1 to Splenic Capsule Boosts Spleen Contraction and Exercise Endurance","authors":"Jing Lou,&nbsp;Mingzong Yang,&nbsp;Yang Hu,&nbsp;Xuyun Liu,&nbsp;Han Li,&nbsp;Zihang Feng,&nbsp;Yuxin Xi,&nbsp;Changyang Xing,&nbsp;Lijun Yuan,&nbsp;Jia Li,&nbsp;Shengpeng Wang,&nbsp;Feng Gao,&nbsp;Xing Zhang","doi":"10.1002/jev2.70375","DOIUrl":"10.1002/jev2.70375","url":null,"abstract":"<p>Haemodynamic shear stress, sensed by vascular endothelial cells (ECs), is crucial for the functional integrity of ECs and the systemic benefits of exercise. Here, we observed that shear stress triggers the release of medium/large extracellular vesicles (m/lEVs), from ECs via activation of the mechanosensitive ion channel Piezo1. Endothelial Piezo1 activation induces Piezo1 translocation to the cell periphery, facilitating its trafficking from the vascular ECs to the smooth muscle cells in the splenic capsule. Within the splenic capsule, the translocated Piezo1 acts as a downstream effector of α1-adrenergic receptor, boosting exercise-induced spleen contraction and enhancing exercise endurance. Genetic or pharmacological inhibition of Piezo1 trafficking from ECs impaired spleen contraction during exercise and reduced exercise endurance in mice. Additionally, exercise-induced m/lEV release contributes to safeguard endothelial function through modulating intracellular Piezo1 homeostasis. Furthermore, positive correlations between exercise-induced increases in circulating Piezo1-enriched m/lEVs and the degree of spleen contraction were also observed in human volunteers. These findings unveil a vasculo-splenic axis during exercise, in which EC-derived m/lEVs shuttle Piezo1 to maintain endothelial function and exercise endurance, highlighting a novel role of Piezo1 in inter-organ communication.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori Outer Membrane Vesicles Engage TLR2 Through NapA to Promote Epithelial Association and Inflammatory Signalling","authors":"Mariaignacia Rubilar,&nbsp;Rosy Brito,&nbsp;Annegrett Palavecino,&nbsp;Joan Villena,&nbsp;Marco Mellado,&nbsp;María I. Silva,&nbsp;Manuel Valenzuela-Valderrama","doi":"10.1002/jev2.70376","DOIUrl":"10.1002/jev2.70376","url":null,"abstract":"<p><i>Helicobacter pylori</i> infection is characterized by chronic gastric inflammation driven by persistent activation of innate immune signalling pathways. Outer membrane vesicles (OMVs) released by <i>H. pylori</i> are important mediators of host–pathogen interactions. Although several mechanisms of OMV internalization have been described, how specific OMV-associated bacterial factors engage host innate immune receptors and couple vesicle association to inflammatory signalling remains poorly understood. Here, we investigated the contribution of OMV-associated virulence factors and Toll-like receptor 2 (TLR2) heterodimers to OMV–host cell interactions in gastric epithelial cells. Using engineered AGS and GES-1 reporter cells expressing TLR2/1 or TLR2/6, together with genetically defined OMVs, we found that <i>H. pylori</i> OMVs preferentially associated with TLR2-expressing cells and induced robust NF-κB activation. Comparative analysis of OMVs from wild-type and isogenic mutant strains identified Neutrophil-Activating Protein A (NapA) as a major determinant of TLR2-dependent OMV association and inflammatory signalling, whereas urease had a more limited contribution. Disruption of NapA or neutralization of TLR2 markedly reduced OMV association with gastric epithelial cells. Purified <i>H. pylori</i> lipopolysaccharide elicited a comparatively weak and TLR2/6-biased response, indicating that it does not account for the robust TLR2-dependent signalling induced by intact OMVs. Furthermore, OMV-associated NapA exhibited greater pro-inflammatory activity than soluble recombinant NapA, supporting a role for the vesicular context in enhancing TLR2-dependent signalling. Pharmacological inhibition with sulforaphane significantly attenuated OMV-induced TLR2/NF-κB activation. Collectively, these findings identify a previously unrecognized role for OMV-associated NapA in linking TLR2-dependent vesicle association with gastric epithelial cells to inflammatory signalling and support a model in which vesicular presentation</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle-Encapsulated Small RNAs From Clostridium Butyricum Modulate Host Intestinal Lipid Metabolism","authors":"Hong Hu,&nbsp;Yiwen He,&nbsp;Jing Liang,&nbsp;Qi Han,&nbsp;Xuqing Liang,&nbsp;Guangtian Cao,&nbsp;Yulong Tang,&nbsp;Liuqin He,&nbsp;Yulong Yin,&nbsp;Xihong Zhou","doi":"10.1002/jev2.70381","DOIUrl":"10.1002/jev2.70381","url":null,"abstract":"<p>The gut microbiota plays a critical role in regulating intestinal lipid metabolism, yet the mechanisms governing microbiota–host interactions during lipid uptake remain unclear. Here, we examined the relationship between fat digestibility and gut microbial composition, and found that piglets with higher apparent crude fat digestibility exhibited enhanced lipid absorption and oxidation, accompanied by reduced abundance of <i>Clostridium butyricum</i> in the ileal mucosa. Furthermore, oral administration of <i>C. butyricum</i> suppressed intestinal lipid absorption and oxidation by inhibiting PPARα signaling. Mechanistically, extracellular vesicles (EVs) derived from <i>C. butyricum</i> can enter intestinal epithelial cells and mediate the anti-lipid absorption effects by delivering miRNA-like RNAs (milRNAs), particularly milRNA-3020179, which primarily targeted host genes including <i>PPARα</i> and <i>Rxra</i>. Supplementation with <i>C. butyricum</i> or its EVs prevented lipid accumulation and attenuated the development of metabolic abnormalities in high-fat diet-fed mice, whereas deletion of milRNA-3020179 in <i>C. butyricum</i> abolished its effects on lipid deposition in intestinal organoids. Collectively, these findings identify <i>C. butyricum</i>-derived EV milRNAs as candidate microbial regulators of host lipid metabolism through modulation of PPARα signaling, providing insights into microbiota-driven control of intestinal lipid homeostasis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trophoblast Extracellular Vesicles Rewire Immunity: A Symptom-Relief Avenue for Recessive Dystrophic Epidermolysis Bullosa","authors":"Nell Hirt,&nbsp;Enzo Manchon,&nbsp;Ming Wu,&nbsp;Helene Le Buanec,&nbsp;Pauline Bataille,&nbsp;Emmanuelle Bourrat,&nbsp;Jean-David Bouaziz,&nbsp;Nabila Jabrane-Ferrat,&nbsp;Reem Al-Daccak","doi":"10.1002/jev2.70315","DOIUrl":"https://doi.org/10.1002/jev2.70315","url":null,"abstract":"<p>Redirecting immune responses toward tissue repair represents a promising strategy for treating inflammatory and degenerative diseases. Extracellular vesicles (EVs), derived from allogeneic stem cells, have shown potential for modulating proinflammatory immunity. Among these, placental-derived EVs (PEVs) are emerging as candidates for immune-mediated inflammatory disorders due to their role in establishing maternal immune tolerance. However, their applicability beyond pregnancy remains limited by key translational barriers, including the lack of a standardized and scalable source system and need to demonstrate immunomodulatory activity in non-pregnancy allogeneic contexts. In this study, we identify extravillous trophoblasts (EVTs), which play critical role in early placental development, as key source of immunoregulatory PEVs. To overcome donor variability, we employed the HIPEC cell model as established surrogate for primary EVTs and assessed the effects of their derived EVs (EVT-EVs) on circulating monocytes, pivotal mediators of inflammatory responses. High-dimensional molecular profiling revealed that EVT-EVs, similar to EVs derived from first-trimester primary human trophoblast, carry a distinctive anti-inflammatory signature, including a unique miRNA repertoire enriched in immunoregulatory pathways. Integrated proteomic and lipidomic analyses demonstrated that EVT-EVs induce coordinated functional reprograming of monocytes toward an immunomodulatory, inflammation-resolving phenotype. Notably, EVT-EVs also modulated the inflammatory bias of monocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB), a genetic disorder characterized by chronic inflammation, thereby promoting restoration of immune balance. Collectively, these findings identify EVT-EVs as a scalable, off-the-shelf platform with high translational potential for the treatment of chronic inflammatory diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 10","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxylipins-Omics Combine With Single-Molecule Analysis Identifies 13(S)-HODE Positive Extracellular Vesicles as a Diagnostic Biomarker for AFP-Negative Hepatocellular Carcinoma","authors":"Yu Wang,&nbsp;Qiaoting Wu,&nbsp;Huixian Lin,&nbsp;Xiaoqing Jiang,&nbsp;Zhenxun Wang,&nbsp;Chao Yang,&nbsp;Rong Wang,&nbsp;Bo Ma,&nbsp;Yingxue Shen,&nbsp;Jiawei Li,&nbsp;Jiaming Chen,&nbsp;Wanyang Sun,&nbsp;Rongrong He,&nbsp;Lei Zheng,&nbsp;Chunchen Liu,&nbsp;Xin Zhang","doi":"10.1002/jev2.70368","DOIUrl":"10.1002/jev2.70368","url":null,"abstract":"<p>Efficient diagnostic biomarkers enable early detection of hepatocellular carcinoma (HCC), which improves survival. Circulating extracellular vesicles (EVs) in plasma, as a noninvasive diagnostic carrier, have caused widely concern. Here, a novel oxylipidomic profiling was used to analysis the HCC patients’ tissue-derived EVs (TD-EVs) cargo and revealing differentially expressed oxylipins (vs. adjacent tissues, <i>p</i>&lt;0.05), which undetected in bulk tissues. The hub oxylipins 13(S)-HODE discovered in TD-EVs was validated in plasma derived EVs (PD-EVs) by using single-molecule analysis platform, showing superior efficacy in AFP-negative HCC patients (AUC = 0.8474 vs. 0.7627 in AFP-positive). Clinically, machine learning integrating EV-derived 13(S)-HODE with routine clinical parameters of HCC patients was developed to optimize diagnostic classification. The machine learning model, LightGBM, achieved outstanding performance: AUC_mean = 0.962, Sensitivity = 0.933 (0.660–0.997), Specificity: 0.957(0.760–0.998), 95%CI: 0.958–1.000 in multi-group classification of HCC diagnostics, demonstrating the enhanced diagnostic efficiency of 13(S)-HODE positive EV subpopulation with other clinical data. This study firstly establishes EV-derived 13(S)-HODE as a concordantly biomarker across tissue and plasma sources. Furthermore, single-molecule analysis platform offers it a highly sensitive diagnostic performance for HCC, particularly valuable for AFP-negative HCC subgroup.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Stem Cell-Derived Extracellular Vesicles Improve CNS Delivery and Therapeutic Efficacy of Antisense Oligonucleotide in Amyotrophic Lateral Sclerosis","authors":"Yaochao Zheng,&nbsp;Taylor Jade Ellison,&nbsp;Robert Garrard,&nbsp;Jinghui Gao,&nbsp;Xinning Lai,&nbsp;Lin Lan,&nbsp;Jin Xie,&nbsp;Jie Jiang,&nbsp;Yao Yao","doi":"10.1002/jev2.70370","DOIUrl":"10.1002/jev2.70370","url":null,"abstract":"<p>Antisense oligonucleotides (ASOs) hold clinical promise for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Yet, their efficacy is constrained by the need for invasive delivery, poor central nervous system (CNS) penetration, inefficient cellular uptake and rapid clearance. Here, we developed neural stem cell-derived extracellular vesicles (NSC-EVs) as natural carriers to enhance CNS targeting and therapeutic efficacy of ASO-based treatments for ALS. Using a passive loading method, therapeutic ASOs were efficiently associated with NSC-EVs (NSC-EV-ASO). Compared with free ASOs, NSC-EVs- ASOs exhibited markedly enhanced neuronal uptake in vitro and increased CNS accumulation and neuronal localization in vivo following intracerebroventricular, intranasal, or intravenous administration. Functionally, NSC-EV-ASOs reduced the mutant SOD1 protein expression and the pathogenic hexanucleotide repeats in the <i>C9orf72</i> loci in ALS cellular models. In the ALS mouse model, intranasal administration of NSC-EV-ASOs more efficiently delayed disease onset, improved motor performance, preserved motor neurons and attenuated astrocyte activation during the study period compared with free ASOs. These findings provide proof-of-concept evidence supporting the potential of NSC-EV as a promising platform that not only enhances CNS delivery of ASOs but also contributes to overall therapeutic activity, offering a synergistic strategy to advance nucleic acid therapeutics for ALS and potentially other neurological diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Product-Derived Vesicles in Nanotherapeutics","authors":"Kartiko Arif Purnomo,&nbsp;Tsong-Long Hwang","doi":"10.1002/jev2.70367","DOIUrl":"10.1002/jev2.70367","url":null,"abstract":"<p>Natural product-derived vesicles (NPVs) are lipid bilayer-enclosed nanovesicles isolated from diverse sources, including plants, fungi, and marine organisms, and are increasingly recognized as an emerging class of extracellular vesicles with potential therapeutic relevance. Their abundance, renewability, and capacity to transport endogenous metabolites and exogenous cargoes highlight their potential as scalable biological delivery vehicles. NPVs can interact with mammalian cells, participate in intercellular communication, and influence conserved biological pathways that modulate disease, support tissue repair, and maintain cellular homeostasis. In addition, their structural plasticity provides opportunities for physicochemical optimization to improve functional performance and targeting properties. However, the development and translation of NPVs are constrained by challenges, including heterogeneity, variability in isolation procedures, and insufficient physicochemical and functional characterization. This review presents a systematic framework encompassing source identification, purification strategies, and characterization methods, while integrating separation approaches with multifaceted assessments to facilitate the rational development of NPVs, with particular emphasis on recent advances in structural optimization and therapeutic efficacy. Furthermore, the status of nine clinical trials is highlighted, reflecting the growing translational and therapeutic potential of NPVs. By delineating current limitations and discussing potential solutions, this review provides practical guidance for improving the physicochemical consistency and biological performance of NPVs, thereby facilitating their development as nature-inspired nanotherapeutic systems.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered Extracellular Vesicles Mitigate Neuroinflammation by Neutralizing Pneumolysin and Delaying Disease Onset in Experimental Pneumococcal Meningitis","authors":"Kristine Farmen,&nbsp;Doste R. Mamand,&nbsp;Miguel Tofiño-Vian,&nbsp;Georgia Yfanti,&nbsp;Xiuming Liang,&nbsp;Houze Zhou,&nbsp;Vicky W. Q. Hou,&nbsp;Samir El Andaloussi,&nbsp;Oscar P. B. Wiklander,&nbsp;Federico Iovino","doi":"10.1002/jev2.70369","DOIUrl":"10.1002/jev2.70369","url":null,"abstract":"<p>Bacterial meningitis is a life-threatening neurological disorder frequently caused by a <i>Streptococcus pneumoniae</i> (the pneumococcus) infection of the brain. Standard treatment consists of antibiotics to eliminate bacteria and dexamethasone to reduce inflammation. Despite this, mortality reaches 20% in treated individuals, and half of the survivors suffer long-term neurological sequelae. This is largely due to the poor capacity of antibiotics to reach the brain and the lack of antimicrobial treatment capable of neutralizing the pneumococcal toxin pneumolysin (Ply). To address these limitations, we isolated extracellular vesicles (EVs) derived from human HEK293T cells and evaluated their therapeutic potential in pneumococcal meningitis. Alongside wild-type EVs (WT.EVs), we bioengineered EVs to express RVG peptides (RVG.EV) for targeting neuronal acetylcholine receptors, signal incompetent IL-6 signal transducer (IL-6ST) decoy receptors (IL-6.EV) to block the pro-inflammatory signalling of IL-6, or EVs expressing both RVG peptides and IL-6ST (DB.EV). <i>In vitro</i>, all EVs reduced pneumococcal adhesion to neurons and mitigated cytotoxicity by binding and sequestering Ply. In a bacteremia-derived pneumococcal meningitis model, EV treatment significantly increased the survival of the mice without affecting bacterial load in the brain or the periphery. Among all groups, RVG.EV treatment was most effective in reducing pro-inflammatory cytokine release in the periphery and brain. These findings highlight the therapeutic potential of bioengineered EVs, particularly RVG peptides expressing EVs, as an adjunctive treatment for pneumococcal meningitis thanks to their (i) sequestration and neutralization of Ply, (ii) increased blood-brain barrier crossing, and (iii) dampening of inflammation.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}