Journal of Extracellular Vesicles最新文献

{"title":"Pyroptosis-Amplified Decoy Nanovesicles Orchestrate Pyroptotic Antigen Explosion and Endogenous Immune Revitalization for Potentiating Tumour Immunotherapy","authors":"Geng Dou,&nbsp;Jiani Liu,&nbsp;Ran Tian,&nbsp;Keying Zhang,&nbsp;Meng Suo,&nbsp;Ding Zhou,&nbsp;Yipeng Zhang,&nbsp;Xuemei Liu,&nbsp;Xinyu Qiu,&nbsp;Jinxin Kuang,&nbsp;Zhaonan Zou,&nbsp;Shuchang Wang,&nbsp;Lu Zhao,&nbsp;Feng Ding,&nbsp;Di Wang,&nbsp;Congcong Guan,&nbsp;Xiaoyu Zhu,&nbsp;Dongyao Wang,&nbsp;Siying Liu,&nbsp;Tianfu Zhang,&nbsp;Yimin Zhao,&nbsp;Shiyu Liu","doi":"10.1002/jev2.70356","DOIUrl":"https://doi.org/10.1002/jev2.70356","url":null,"abstract":"<p>Current advances in tumour immunotherapy remain constrained by inadequate cytotoxic T lymphocyte activation and the immunosuppressive tumour microenvironment. Innovative strategies are urgently required to enhance anti-tumour immune potency for clinical improvements in immunotherapy-resistant malignancies. Herein, we developed pyroptosis-amplified decoy nanovesicles (PADVs) to synergistically dismantle tumour resistance mechanisms and rejuvenate endogenous anti-tumour immunity. PADVs integrate checkpoint-neutralizing capability with precise regulation of the pyroptosis molecular switch in tumour cells, thereby initiating a sequential activation cascade that enables efficient presentation of tumour-specific antigens to the reshaped immune system. Systemically infused PADVs demonstrated dual-targeting priority towards lymph node and deep tumour tissues, reversing immunosuppression through competitive blockade of PD-1/PD-L1 and SIRPα/CD47 axes while providing co-stimulatory signals for immune reactivation. Furthermore, PADVs alleviate the epigenetic suppression of pyroptosis in tumours via cytosolic delivery of decitabine and LPS, enabling gasdermin D (GSDMD) upregulation and cleavage. This coordinated strategy reverses T cell exhaustion and triggers explosive antigen release via GSDMD-mediated membrane perforation, initiating a self-amplifying immune cascade involving dendritic cell activation, effector and memory T cell formation. Consequently, PADVs demonstrate excellent efficacy in suppressing tumour progression, recurrence, and metastasis in melanoma, breast cancer, and colon cancer models. This study pioneers a versatile nanoplatform that not only counteracts tumour immune evasion but also establishes durable anti-tumour immunity, offering a transformative approach to tumour immunotherapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 9","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823325","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":"NF1 Leucine Rich Domain-Derived Extracellular Vesicles Remodel the Glioblastoma Immune Microenvironment via an ADAM17-Associated Inflammatory Program","authors":"Yuganthini Vijayanathan,&nbsp;Jacqueline YT Yeo,&nbsp;Janice HY Tan,&nbsp;Fikri Bin Mohamed,&nbsp;Bernett Lee,&nbsp;Tatsuya Kozaki,&nbsp;Nurashikin Abdul Halim,&nbsp;Rachel LY Ho,&nbsp;Hai Tao Tu,&nbsp;Zhi Wei Zhang,&nbsp;Jann N. Sarkaria,&nbsp;Li Zeng,&nbsp;Florent Ginhoux,&nbsp;Ivy AW Ho","doi":"10.1002/jev2.70355","DOIUrl":"https://doi.org/10.1002/jev2.70355","url":null,"abstract":"<p>Extracellular vesicles (EVs) are increasingly recognized as mediators of intercellular communication in cancer. We previously demonstrated that re-expression of the leucine-rich domain (LRD) of neurofibromin (NF1) suppresses glioblastoma (GBM) invasion and limits microglia/macrophage infiltration into the tumor microenvironment (TME). Given the central role of tumor-associated microglia/macrophages (TAMs) in GBM progression, we investigated whether NF1-LRD-containing EVs (NF1-LRD-EVs) could modulate TAM function and remodel the TME. Our results showed that NF1-LRD-EVs attenuated microglia and macrophage recruitment in migration assays, consistent with reduced microglia/macrophage recruitment observed <i>in vivo</i>. In parallel, treatment with NF1-LRD-EVs enhanced phagocytic activity of both microglia and iPSC-derived macrophages, accompanied by induction of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and downregulation of immunosuppressive mediators such as Arginase-1 and IL-10. Mechanistically, NF1-LRD-EVs induced ADAM17-associated inflammatory signaling, accompanied by NF-κB activation. Pharmacological inhibition of ADAM17 reduced TNF-α release and attenuated NF-κB activation, supporting a role for ADAM17-dependent signaling in amplifying this inflammatory response. Together, these findings show that NF1-LRD-EVs reprogram TAMs toward a pro-inflammatory phenotype and modulate the GBM immune microenvironment. These results provide a framework for understanding NF1-LRD-EV-mediated immune regulation and support further investigation of EV-mediated immune modulation of the TME.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785018","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":"NF1 Leucine Rich Domain-Derived Extracellular Vesicles Remodel the Glioblastoma Immune Microenvironment via an ADAM17-Associated Inflammatory Program","authors":"Yuganthini Vijayanathan,&nbsp;Jacqueline YT Yeo,&nbsp;Janice HY Tan,&nbsp;Fikri Bin Mohamed,&nbsp;Bernett Lee,&nbsp;Tatsuya Kozaki,&nbsp;Nurashikin Abdul Halim,&nbsp;Rachel LY Ho,&nbsp;Hai Tao Tu,&nbsp;Zhi Wei Zhang,&nbsp;Jann N. Sarkaria,&nbsp;Li Zeng,&nbsp;Florent Ginhoux,&nbsp;Ivy AW Ho","doi":"10.1002/jev2.70355","DOIUrl":"https://doi.org/10.1002/jev2.70355","url":null,"abstract":"<p>Extracellular vesicles (EVs) are increasingly recognized as mediators of intercellular communication in cancer. We previously demonstrated that re-expression of the leucine-rich domain (LRD) of neurofibromin (NF1) suppresses glioblastoma (GBM) invasion and limits microglia/macrophage infiltration into the tumor microenvironment (TME). Given the central role of tumor-associated microglia/macrophages (TAMs) in GBM progression, we investigated whether NF1-LRD-containing EVs (NF1-LRD-EVs) could modulate TAM function and remodel the TME. Our results showed that NF1-LRD-EVs attenuated microglia and macrophage recruitment in migration assays, consistent with reduced microglia/macrophage recruitment observed <i>in vivo</i>. In parallel, treatment with NF1-LRD-EVs enhanced phagocytic activity of both microglia and iPSC-derived macrophages, accompanied by induction of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and downregulation of immunosuppressive mediators such as Arginase-1 and IL-10. Mechanistically, NF1-LRD-EVs induced ADAM17-associated inflammatory signaling, accompanied by NF-κB activation. Pharmacological inhibition of ADAM17 reduced TNF-α release and attenuated NF-κB activation, supporting a role for ADAM17-dependent signaling in amplifying this inflammatory response. Together, these findings show that NF1-LRD-EVs reprogram TAMs toward a pro-inflammatory phenotype and modulate the GBM immune microenvironment. These results provide a framework for understanding NF1-LRD-EV-mediated immune regulation and support further investigation of EV-mediated immune modulation of the TME.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785017","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":"Small Extracellular Vesicle-Derived Nidogen 1 Promotes HCC Carcinogenesis via Transglutaminase 3-Mediated YAP/TAZ Signalling","authors":"Cherlie Lot Sum Yeung,&nbsp;Le Cui,&nbsp;Jingyi Wang,&nbsp;Ching-Ping Chan,&nbsp;Tung Him Ng,&nbsp;Charlotte Jiaqi Lai,&nbsp;Xiaowen Mao,&nbsp;Sze Keong Tey,&nbsp;Michael Shing Yan Huen,&nbsp;Judy Wai Ping Yam","doi":"10.1002/jev2.70359","DOIUrl":"10.1002/jev2.70359","url":null,"abstract":"<p>Tumour-derived small extracellular vesicles (sEV) are increasingly recognized as key mediators of cancer progression and metastasis by facilitating intercellular communication. In this study, we identify nidogen 1 (NID1), a basement membrane glycoprotein, as significantly enriched in sEV from metastatic hepatocellular carcinoma (HCC) cells. We demonstrate that the sEV-mediated delivery of NID1 enhances oncogenic behaviours, including proliferation, invasion and metastasis. Knockout mice of NID1 exhibited a marked delay in liver tumour formation induced by N-diethylnitrosamine (DEN) and carbon tetrachloride (CCL4), or hydrodynamic injection delivery of oncogenes, underscoring the role of NID1 in hepatocarcinogenesis. Importantly, we find that a stiffer extracellular matrix, a characteristic of tumour microenvironments, stimulates increased NID1 level in sEV. Using NID1 mutants, we identify the C-terminal domain as critical for its oncogenic functions, including promoting tumour growth and metastasis. Proteomic profiling reveals that transglutaminase 3 (TGM3) interacts with NID1 via its C-terminus. Subsequent analyses indicate that sEV-NID1 elevates TGM3 levels, leading to dysregulation of integrins and activation of the YAP/TAZ signalling pathway, thereby contributing to tumour progression. To explore therapeutic potential, we developed a novel monoclonal anti-NID1 antibody (anti-NID1 mAb) and evaluated its efficacy in multiple HCC mouse models. The antibody markedly suppressed liver tumour growth and metastasis of human and murine HCC cells. The therapeutic effect was further enhanced when combined with sorafenib, a standard treatment for HCC. Our findings delineate a novel sEV-NID1-TGM3 regulatory axis that promotes hepatocarcinogenesis and metastasis and suggest that targeting sEV-delivered NID1 with our homemade monoclonal antibody offers a promising avenue for therapeutic intervention in HCC.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759674","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":"Regulatory Science of Extracellular Vesicles: From ISEV Standards to Translational Implementation (Insights From Japan)","authors":"Yusuke Yoshioka,&nbsp;Yu Fujita,&nbsp;Takahiro Ochiya","doi":"10.1002/jev2.70358","DOIUrl":"10.1002/jev2.70358","url":null,"abstract":"<p>Extracellular vesicles (EVs) offer compelling opportunities for diagnostics and therapeutics, yet translation toward routine clinical use and commercial readiness remains limited. In diagnostics, EV-based assays may reach practice as laboratory-developed tests, while in therapeutics unproven “exosome” offerings have prompted safety communications, together underscoring the need for fit-for-purpose regulatory science. Here, we organize implementation challenges into six recurring bottlenecks: Identity; Purity; Potency; Measurement comparability; Manufacturing control; and Safety. We summarize how international standardization efforts led by the International Society for Extracellular Vesicles (ISEV), including MISEV2023 and task-force outputs, strengthen reproducibility and comparability, while highlighting remaining gaps that arise when descriptive guidance must be converted into operational specifications and submission-ready evidence packages. Using Japan as a case example, we illustrate how regulatory-authority discussions, professional-society statements, and emerging implementation-oriented guidance can clarify review questions, distinguish therapeutic EV products from conditioned medium, and support trust-preserving translation. Finally, we propose a non-binding, deliverables-based roadmap across near-, mid-, and long-term horizons to enable clinical and commercial readiness. The roadmap should be adapted to product context, risk profile, and jurisdiction, and it emphasizes precompetitive collaboration across academia, industry, and government to build shared infrastructure for measurement, standardization, reproducibility, and quality evaluation, thereby translating scientific consensus into operational development and review frameworks.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758797","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":"Vesicle Nucleation Peptide Fusion Induced Extracellular Vesicles Are Distinct From Escherichia coli Outer Membrane Vesicles, and Provide an Enhanced Platform for Protein Production and Purification","authors":"Bree R. Streather,&nbsp;Tara A. Eastwood,&nbsp;Karen Baker,&nbsp;Mingzhi Liang,&nbsp;Alexandra E. Bailie,&nbsp;Tijn T. van der Velden,&nbsp;Lars J. C. Jeuken,&nbsp;Stanley W. Botchway,&nbsp;Lin Wang,&nbsp;Daniel P. Mulvihill","doi":"10.1002/jev2.70354","DOIUrl":"https://doi.org/10.1002/jev2.70354","url":null,"abstract":"<p>Bacterial outer membrane vesicles (OMVs) are nano-sized, spherical structures released by Gram-negative bacteria that play diverse roles in bacterial physiology, including communication, nutrient acquisition and host interactions. These vesicles bud from the bacterial outer membrane and contain lipopolysaccharides, periplasmic proteins, nucleotides and other biomolecules. The vesicle nucleating peptide (VNp) is a short peptide tag that, when fused to the amino terminus of a protein of interest, promotes the formation of bespoke recombinant extracellular vesicles (EVs) in <i>Escherichia coli</i>, enabling efficient production and simplified purification of recombinant proteins. Here, we characterise VNp-induced extracellular vesicles (VNp-EVs) and compare their composition and organisation with OMVs produced from <i>E. coli</i> expressing a periplasmic targeting fusion. While both vesicle types possess a single outer membrane-derived lipid bilayer, recombinant protein is highly enriched within the VNp-EVs compared to OMVs containing the periplasm targeting ssDsbA-fusion protein. VNp-fusions and the periplasm-targeted recombinant protein localise to distinct vesicle populations, with VNp-fusions showing markedly higher luminal concentrations and relative vesicular abundance, compared to the vesicles containing a periplasmic targeted fusion protein. OmpX co-expression further enriched the VNp-fusion content of vesicles, further enhancing yield. The VNp-vesicle lumen is an oxidising environment, thus supports formation of inter- and intra-molecular disulfide bonds within encapsulated proteins. Overall, VNp-EVs represent a distinct class of recombinant EVs that offer a simple and efficient route for producing and purifying concentrated, correctly folded recombinant proteins, expanding the utility of bacterial vesicle systems for biotechnological applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753851","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":"Vesicle Nucleation Peptide Fusion Induced Extracellular Vesicles Are Distinct From Escherichia coli Outer Membrane Vesicles, and Provide an Enhanced Platform for Protein Production and Purification","authors":"Bree R. Streather,&nbsp;Tara A. Eastwood,&nbsp;Karen Baker,&nbsp;Mingzhi Liang,&nbsp;Alexandra E. Bailie,&nbsp;Tijn T. van der Velden,&nbsp;Lars J. C. Jeuken,&nbsp;Stanley W. Botchway,&nbsp;Lin Wang,&nbsp;Daniel P. Mulvihill","doi":"10.1002/jev2.70354","DOIUrl":"https://doi.org/10.1002/jev2.70354","url":null,"abstract":"<p>Bacterial outer membrane vesicles (OMVs) are nano-sized, spherical structures released by Gram-negative bacteria that play diverse roles in bacterial physiology, including communication, nutrient acquisition and host interactions. These vesicles bud from the bacterial outer membrane and contain lipopolysaccharides, periplasmic proteins, nucleotides and other biomolecules. The vesicle nucleating peptide (VNp) is a short peptide tag that, when fused to the amino terminus of a protein of interest, promotes the formation of bespoke recombinant extracellular vesicles (EVs) in <i>Escherichia coli</i>, enabling efficient production and simplified purification of recombinant proteins. Here, we characterise VNp-induced extracellular vesicles (VNp-EVs) and compare their composition and organisation with OMVs produced from <i>E. coli</i> expressing a periplasmic targeting fusion. While both vesicle types possess a single outer membrane-derived lipid bilayer, recombinant protein is highly enriched within the VNp-EVs compared to OMVs containing the periplasm targeting ssDsbA-fusion protein. VNp-fusions and the periplasm-targeted recombinant protein localise to distinct vesicle populations, with VNp-fusions showing markedly higher luminal concentrations and relative vesicular abundance, compared to the vesicles containing a periplasmic targeted fusion protein. OmpX co-expression further enriched the VNp-fusion content of vesicles, further enhancing yield. The VNp-vesicle lumen is an oxidising environment, thus supports formation of inter- and intra-molecular disulfide bonds within encapsulated proteins. Overall, VNp-EVs represent a distinct class of recombinant EVs that offer a simple and efficient route for producing and purifying concentrated, correctly folded recombinant proteins, expanding the utility of bacterial vesicle systems for biotechnological applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753865","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":"Stress-Induced Switch in Small Extracellular Vesicle Secretion: From Constitutive ‘Torn Bag Mechanism’ to Exocytosis","authors":"Dorina Lenzinger,&nbsp;Lilla Lankovics,&nbsp;István Dudás,&nbsp;Tünde Bárkai,&nbsp;Zsófia Szász,&nbsp;Mirjam Balbisi,&nbsp;Anthony Yan-Tang Wu,&nbsp;Krisztina V. Vukman,&nbsp;Kelsey Fletcher,&nbsp;Attila Csomos,&nbsp;Zoltán Mucsi,&nbsp;Edina Bugyik,&nbsp;Csaba Cserép,&nbsp;Ádám Dénes,&nbsp;Szilvia Bősze,&nbsp;Lilla Turiák,&nbsp;Charles Pin-Kuang Lai,&nbsp;Edit I. Buzás,&nbsp;Tamás Visnovitz","doi":"10.1002/jev2.70345","DOIUrl":"10.1002/jev2.70345","url":null,"abstract":"<p>The biogenesis of small extracellular vesicles (sEVs) is only partially understood. Our recent findings provide evidence that a newly described sEV secretion pathway, the amphiectosome release followed by the sEV discharge by the ‘torn bag mechanism’ are present in all tested cell lines and mouse organs. Surprisingly, in in situ fixed steady-state cells, transmission electron microscopy did not reveal sEV release via exocytosis of multivesicular endosomes (MVEs). In the current study, we extended our previous analysis to additional mouse organs and confirmed the presence of secreted amphiectosomes in all of them. Furthermore, we investigated which parameters influence the activation of the distinct sEV release mechanisms in HEK cells. Our results show that under stress conditions (such as Ca²⁺ ionophore-induced membrane stress or metabolic stress, induced by serum starvation), exocytosis of MVEs is activated, while this process is absent in steady-state conditions. By silencing ATG5 (a key regulator of autophagy) and RAB27a (an essential small GTPase for MVE exocytosis), we selectively modulated these two mechanisms, respectively. Amphiectosome release depended on both autophagy and ATG5, while exocytosis of MVE was autophagy-independent but RAB27a-dependent. Our findings suggest that sEV release via the ‘torn bag mechanism’ is a general and essential secretion pathway in non-stressed, steady-state mammalian cells, while stress conditions induce the sEV release via MVE exocytosis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712716","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":"Tumour-Derived Extracellular Vesicles Containing dsRNA Induce Degradation of Ribosomal Protein mRNA in Platelets","authors":"Gaoge Sun,&nbsp;Yuhuan Tao,&nbsp;Zihan Liu,&nbsp;Kaixiang Zhang,&nbsp;Shuai Zuo,&nbsp;Shanwen Chen,&nbsp;Shufang Ning,&nbsp;Tianyi Zhang,&nbsp;Pengyuan Wang,&nbsp;Ying Zhang,&nbsp;Zhi John Lu,&nbsp;Hang Hubert Yin","doi":"10.1002/jev2.70339","DOIUrl":"10.1002/jev2.70339","url":null,"abstract":"<p>Extracellular vesicles (EVs) mediate intercellular communication within the tumour microenvironment by carrying cargoes from paracrine parent cells. EVs have attracted great research interest for their ability to carry nucleic acids into recipient cells and modulate cellular functions. However, previous studies have largely focused on RNA sequence information rather than RNA structure features. Here, we observed that EVs derived from colorectal cancer cells are enriched with endogenous double‑stranded RNA (dsRNA), a danger‑associated molecular pattern (DAMP) that leads to the activation of dsRNA‑sensing pathways in recipient cells. Crucially, we investigated the specific crosstalk between tumour-derived EVs and circulating platelets. As anucleate cells, platelets are uniquely suited models for isolating the effects of exogenous nucleic acids. Our analysis reveals that endogenous dsRNA from tumour EVs activates the platelet OAS–RNASEL innate immune ribonuclease cascade and the RNASEL/ABCE1/PELO axis, resulting in the decay of ribosomal protein mRNAs. This study, spanning from clinical observation to mechanistic validation, uncovers a novel pathway of tumour–platelet communication. We identify EV-enriched endogenous dsRNA as a functional mediator that enables tumour cells to directly reprogram platelet transcriptomes, revealing a new dimension of tumour–immune modulation.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701408","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":"Camouflage Protein-Engineered Extracellular Vesicles Alleviate TMJ-OA by Hijacking Caspase-1 to Suppress Pyroptosis","authors":"Yufei Liu,&nbsp;Jie Zhou,&nbsp;Yukang Wang,&nbsp;Zhihui Hu,&nbsp;Guimin Yin,&nbsp;Mengsen Zhu,&nbsp;Jianke Huo,&nbsp;Chenyang Zhang,&nbsp;Yiming Wang,&nbsp;Shuang Fu,&nbsp;Jinpeng Wan,&nbsp;Jie Wang,&nbsp;Lanju Xu,&nbsp;Zhiling Zhang,&nbsp;Shufang Wang","doi":"10.1002/jev2.70342","DOIUrl":"10.1002/jev2.70342","url":null,"abstract":"<p>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 <i>in vitro</i> 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.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701214","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}