Extracellular vesicles and circulating nucleic acids最新文献

{"title":"A multidimensional landscape of extracellular vesicle-mediated tumor drug resistance: mechanisms, biomarkers, engineered drug delivery, and clinical translation.","authors":"Zhiqin Fu, Yanting Kuang, Meichai Li, Kexuan Zhou, Hao Shi, Yongwei Gu, Xin Wu, Yizhun Zhu, Jiyong Liu","doi":"10.20517/evcna.2025.184","DOIUrl":"10.20517/evcna.2025.184","url":null,"abstract":"<p><p>Tumor drug resistance is a major clinical challenge that limits the efficacy of chemotherapy, targeted therapy, and immunotherapy, thereby contributing to tumor recurrence, metastasis, and reduced overall patient survival rates. Recent studies reveal that extracellular vesicles (EVs) in the tumor microenvironment act as key mediators of intercellular communication. They play a central role in mediating tumor cell resistance by transporting functional cargo, including RNA, proteins, and lipids. This review outlines the mechanisms of EV-mediated tumor resistance, including key processes such as drug efflux, evasion of apoptosis, maintenance of epithelial-mesenchymal transition and cancer stem cell phenotypes, remodeling of the immune microenvironment, metabolic reprogramming, and expansion of resistant cell populations. It also discusses the use of EVs as biomarkers of resistance and their associated detection technologies. Furthermore, this paper highlights therapeutic strategies for reversing drug resistance through engineered EVs, including the delivery of small molecules, nucleic acid therapeutics, and key bioactive components. It also reviews current preclinical studies and progress toward clinical translation of EV-based resistance reversal strategies. This review aims to elucidate the role and translational potential of EVs in tumor drug resistance through a systematic approach that integrates mechanism exploration, biomarker identification, engineered drug delivery, and clinical translation. It provides a comprehensive reference to facilitate further advances in this field, from basic research to clinical practice.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"614-649"},"PeriodicalIF":8.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of methods for isolation of extracellular vesicles from bronchoalveolar lavage fluid.","authors":"Mark E Fraser, Radha Patel, Taylor Shinabery, John Zagorski, Ling Chen, Navneet K Dhillon, Matthias Clauss, Emma H Doud, Amber L Mosley, Benjamin Gaston, Homer L Twigg Iii","doi":"10.20517/evcna.2025.85","DOIUrl":"10.20517/evcna.2025.85","url":null,"abstract":"<p><p><b>Aim:</b> Extracellular vesicles (EVs) have been described and isolated from a variety of biological samples, including bronchoalveolar lavage (BAL). While EVs have been isolated from BAL by various methods, there has not been a comparative study to determine optimal EV isolation methods for this complex and unique biologically derived fluid. <b>Methods:</b> Membrane affinity binding (exoEasy by Qiagen), ultracentrifugation (UC), and size-exclusion chromatography (SEC) EV isolation methods were compared to determine the best utilization of each method when isolating EVs from BAL. <b>Results:</b> Both SEC and UC were able to isolate significant EV populations reliably, with UC yielding higher apparent yields by western blotting and Nanosight particle tracking. However, transmission electron microscopy, total protein assays, and proteomic analysis suggested this was due to free protein and protein aggregate contamination. The exoEasy kit demonstrated inconsistent yields and protein measurements that were frequently higher than unprocessed BAL samples. Furthermore, ExoEasy preps contained many unique proteins and higher lipoproteins compared to SEC and UC. This may indicate false signal as a result of the EV isolation process making analysis and downstream applications unreliable without an additional buffer exchange step. Most of the protein in BAL was found in the non-EV fractions. In contrast, virtually all the nucleic acids, both RNA and dsDNA, found in BAL were in the protected environment of EVs. <b>Conclusion:</b> SEC fractions containing EVs, when concentrated using 30 kDa centrifugal filters, yielded the lowest contaminating free protein and the highest nucleic acid content. This, coupled with good yield and preservation of EV structure and function for downstream use, makes it the ideal EV isolation protocol from BAL.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"595-613"},"PeriodicalIF":8.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as a novel topical immunomodulatory therapy for psoriasis: bridging the therapeutic gap in moderate disease.","authors":"Thong Teck Tan, Kok Hian Tan, Sai Kiang Lim","doi":"10.20517/evcna.2025.150","DOIUrl":"10.20517/evcna.2025.150","url":null,"abstract":"<p><p>Psoriasis is a chronic, immune-mediated inflammatory disease that affects approximately 2%-3% of the global population, and remains a major dermatologic and psychosocial burden. Despite advances in biologics targeting interleukin 17 (IL-17) and interleukin 23 (IL-23) pathways, effective and accessible treatment options for moderate psoriasis are lacking. Topical therapies and phototherapy are often inadequate, while systemic agents and biologics are limited by toxicity, high cost, and restricted reimbursement criteria, leaving patients with moderate disease without adequate therapeutic options. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising acellular therapeutic modality that harnesses the immunomodulatory and regenerative properties of parent MSCs. Unlike systemic biologics, MSC-EVs act locally and non-immunosuppressively. Topically applied MSC-EVs have demonstrated the ability to modulate cutaneous inflammation by attenuating complement activation [via CD59-mediated inhibition of complement terminal component 5b-9 (C5b-9) complex formation], reducing neutrophil infiltration, and subsequently lowering IL-17 and IL-23 expression in psoriatic lesions. Preclinical and early clinical studies suggest that MSC-EVs can restore local immune homeostasis through paracrine extracellular mechanisms, without systemic absorption or adverse effects. MSC-EVs represent a new class of cell-free nanotherapeutics inspired by biologics, capable of localized immunomodulation in psoriasis. By combining biologic-like efficacy with the safety and accessibility of topical therapy, MSC-EVs may bridge the long-standing therapeutic gap in moderate psoriasis. This review discusses current treatment limitations, the mechanistic rationale for MSC-EVs in psoriatic inflammation, and their potential to redefine dermatologic immunotherapy.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"580-594"},"PeriodicalIF":8.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Rehmannia glutinosa</i> nanovesicles protect cardiomyoblasts from oxidative injury.","authors":"Huilan Fan, Shuang Zhao, Yunfeng Di, Yangyi Yu, Yafei Sun, Yong Wang, Chun Li, Jingyu Wang","doi":"10.20517/evcna.2025.185","DOIUrl":"10.20517/evcna.2025.185","url":null,"abstract":"<p><p><b>Aim:</b> Oxidative stress is a key driver of cardiovascular disease, underscoring the need for safe and effective antioxidant therapies. This study aims to evaluate the cardioprotective potential of plant-derived nanovesicles (PDNVs) derived from <i>Panax ginseng</i> (Gin) and <i>Rehmannia glutinosa</i> (Glu) against hydrogen peroxide (H₂O₂)-induced oxidative injury in cardiac cells. <b>Methods:</b> PDNVs were isolated from medicinal plants via differential ultracentrifugation and characterized for morphology, diameter, stability, and cellular uptake. The antioxidant and cytoprotective effects were assessed in H₂O₂-injured cardiomyoblasts through cell viability, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·) radical scavenging, intracellular reactive oxygen species (ROS) and mitochondrial superoxide detection, and antioxidant enzyme (superoxide dismutase, SOD; glutathione peroxidase, GPx) activity assays. The composition of the PDNVs was determined through Coomassie Brilliant Blue staining for proteins, agarose gel electrophoresis for nucleic acids, and liquid chromatography-mass spectrometry system (LC-MS) for bioactive monomers. <b>Results:</b> Gin-PDNVs and Glu-PDNVs significantly enhanced cardiomyoblast viability under oxidative stress. Glu-PDNVs demonstrated superior efficacy at lower concentrations, with stronger ROS scavenging capacity. Compositional analysis revealed that Glu-PDNVs carry proteins, nucleic acids, and antioxidant herbal compounds such as catalpol, rehmannioside D, and acteoside. Glu-PDNVs also dose-dependently scavenged DPPH· radicals, reduced mitochondrial superoxide accumulation, and significantly restored the H₂O₂-induced suppression of SOD and GPx activities. <b>Conclusion:</b> This study provides the first evidence that Glu-PDNVs exert potent cardioprotection by regulating ROS and superoxide homeostasis, positioning them as a promising natural nanotherapeutic platform with translational potential.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"563-579"},"PeriodicalIF":8.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles as mediators of prostatic diseases: connecting function to diagnostic and therapeutic applications.","authors":"Julie Bishara, Morolake Morakinyo, Sharanjot Saini","doi":"10.20517/evcna.2025.96","DOIUrl":"10.20517/evcna.2025.96","url":null,"abstract":"<p><p>Diseases of the prostate gland, including benign prostatic hyperplasia (BPH) and prostate cancer (PCa), affect a significant proportion of men worldwide. The incidence of these diseases increases with advancing age decreased quality of life and mortality in cases of aggressive PCa. Advanced PCa shows a spectrum of disease states, including castration-resistant prostate cancer (CRPC) and therapy-resistant neuroendocrine prostate cancer (NEPC). NEPC is a highly aggressive, AR-independent state that evolves from CRPC by \"lineage switching\". Although the underlying cellular mechanisms have been examined extensively, the role of extracellular-mediated intercellular communication is less well understood. Emerging evidence suggests an important role of extracellular vesicles (EVs) in the pathobiology of these diseases. EVs have been shown to be critical for imparting tumor aggressiveness via inducing epithelial to mesenchymal transition (EMT), stemness and immune evasion. Understanding EV-mediated signaling that governs the progression of prostatic diseases is crucial for developing effective targeted therapies and robust biomarkers for prognosis and risk stratification. Advances in EV engineering have enabled the development of targeted exosome-based therapeutics capable of delivering drugs, biologic payloads, or immune-stimulating signals. In this article, we review our current knowledge on the role of EVs in prostatic diseases, explore their diagnostic and therapeutic applications, and outline future directions aimed at translating EV-based technologies into tools for improved clinical management.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"545-562"},"PeriodicalIF":8.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel extracellular vesicle isolation method based on cellulose nanofiber sheets.","authors":"Yukari Nagao, Hiroaki Kajiyama, Akira Yokoi","doi":"10.20517/evcna.2025.187","DOIUrl":"10.20517/evcna.2025.187","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) circulate in body fluids, carrying molecular cargo from their parent cells and exerting diverse biological functions. Consequently, they have attracted considerable attention as biomarkers for disease detection and pathophysiological understanding and have emerged as potential therapeutic targets. Although the number of clinical trials involving EVs is increasing, major challenges remain, including methodological transparency and the heterogeneity of EV subpopulations. Various EV isolation methods are commonly employed, and the primary approaches are summarized in the <i>MISEV2023</i> guidelines. Each method has advantages and disadvantages; however, most conventional approaches require relatively large liquid volumes (e.g., hundreds of microliters or more) to obtain sufficient EV yields for analysis. In recent years, novel technologies have been developed to overcome these limitations by addressing constraints related to sample volume, simplicity, and accuracy. One such innovation is the cellulose nanofiber-EV sheet, which we developed in 2023. This method enables the capture and stable storage of EVs from microvolumes of body fluids (e.g., approximately 10 µL). Two application methods are available: the attaching method, in which the EV sheet is applied to moist tissue surfaces, and the soaking method, in which the sheet is soaked into body fluids. Each method offers distinct advantages. Given their unique properties, EV sheets may contribute to biomarker analysis and facilitate new research directions across diverse fields. Continued advances in EV isolation and analytical platforms will be essential to support the safe clinical implementation of EV-based diagnostics and therapeutics.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"535-544"},"PeriodicalIF":8.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial extracellular vesicles in the lung: friends in health, agents in disease.","authors":"Marta Pagnini, Maria Conti, Giorgia Puddu, Matteo Daverio, Alessandro Celi, Erica Bazzan, Tommaso Neri","doi":"10.20517/evcna.2025.139","DOIUrl":"10.20517/evcna.2025.139","url":null,"abstract":"<p><p>Microbial extracellular vesicles (mEVs) are emerging as key mediators at the host-microbe interface in the lung, playing a remarkable dual role as both pathogenic drivers and therapeutic modulators. These nano-sized, membrane-bound structures (20-400 nm) secreted by bacteria, fungi, and other microorganisms carry diverse bioactive cargo including lipids, proteins, and nucleic acids that can profoundly influence host immune responses and tissue homeostasis. mEVs derived from probiotic bacteria demonstrate significant therapeutic potential as immunomodulatory agents capable of reducing pulmonary inflammation and enhancing epithelial barrier function. These probiotic-derived vesicles represent a novel class of postbiotics - bioactive microbial products that confer health benefits without requiring live microbial cells. Conversely, in pathogenic contexts, mEVs from bacteria such as <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i> trigger robust inflammatory responses in the lung through pattern recognition receptor activation, particularly Toll-like receptors (TLRs)-2 and TLR-4, leading to upregulation of pro-inflammatory cytokines and contributing to chronic respiratory conditions including asthma and chronic obstructive pulmonary disease. Given its extensive surface area and highly specialized immune network, the lung represents a highly receptive site for mEV-mediated interactions. This review synthesizes evidence on pathogenic mechanisms of mEVs and explores their therapeutic potential in respiratory medicine, with specific focus on: (1) the role of environmentally-derived mEVs from dust and airborne sources in chronic respiratory inflammation; (2) recent experimental evidence of probiotic-derived mEVs therapeutic effects across diverse pulmonary conditions and (3) the concept of mEVs as both protective postbiotics and inflammatory triggers in the lung.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"514-534"},"PeriodicalIF":8.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verification of the predictive value of EV-associated biomarkers MMP9 and CEACAM1 in rehabilitation of ischemic stroke.","authors":"Jiao Luo, You Cai, Yanling Cai, Chunxia Zhang, Ankang Liu, Yongyang Huo, Xuehui Fan, Ruixue Ye, Hong Gao, Meiling Huang, Xiaohua Zhang, Mingchao Zhou, Yulong Wang","doi":"10.20517/evcna.2025.122","DOIUrl":"10.20517/evcna.2025.122","url":null,"abstract":"<p><p><b>Aim:</b> Extracellular vesicles (EVs) contribute to stroke rehabilitation by mediating intercellular signaling during inflammation and tissue repair. Here we report EV-associated surface proteins as potential biomarkers for predicting recovery of activities of daily living (ADL) during the subacute phase of ischemic stroke (IS). <b>Methods:</b> IS patients and healthy controls (HCs) were recruited for this study, with serum samples analyzed across three study stages. In the discovery subset (10 IS, 6 HCs), serum proteomics was used to identify differentially expressed proteins (DEPros) and perform Gene Ontology (GO) enrichment analysis. In the exploration subset (7 IS, 12 HCs), a proximity-dependent barcoding assay (PBA) was employed to profile surface proteins on individual EVs and screen for biomarker candidates. In a validation cohort, patients were grouped by ADL improvement (little-effect recovery, LE, <i>n</i> = 30; obvious-effect recovery group, OE, <i>n</i> = 22) based on Longshi Scale and Barthel Index assessments at admission and at 3 months follow-up. Targeted biomarker validation was performed with enzyme-linked immunosorbent assay (ELISA) and receiver operating characteristic (ROC) analysis. <b>Results:</b> A total of 113 DEPros were identified, with GO term enrichment in EV-related pathways. PBA profiling revealed matrix metalloproteinase 9 (MMP9), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), melanoma cell adhesion molecule (MCAM), and gelsolin (GSN) as candidate biomarkers. In the validation cohort, MMP9 and CEACAM1 were significantly elevated in the LE group. ROC analysis showed area under the curve (AUC) of 0.726 for MMP9 and 0.700 for CEACAM1 in distinguishing LE from OE. <b>Conclusion:</b> Elevated serum levels of EV-associated biomarkers MMP9 and CEACAM1 were associated with poor ADL recovery, supporting their potential as prognostic biomarkers for stroke rehabilitation outcomes.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"496-513"},"PeriodicalIF":8.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human umbilical cord mesenchymal stem cell-derived nanovesicles ameliorate acute lung injury by hsa-let-7g-5p inhibition of NF-κB/NLRP3 pathway.","authors":"Yilin Huang, Yan Zeng, Ailin Wu, Yang Chen, Yuanhao Zhou, Youni Zhang, Hai Zou, Weijiao Fan, Xiaoyi Chen, Jinyang Chen, Jie Wang, Xianghong Yang, Xiaoru Chang, Xiaozhou Mou, Yuexing Tu","doi":"10.20517/evcna.2025.170","DOIUrl":"10.20517/evcna.2025.170","url":null,"abstract":"<p><p><b>Aim:</b> Acute lung injury (ALI), marked by vigorous inflammatory reactions and elevated incidence, is a grave clinical issue for which efficacious pharmaceutical interventions are still lacking. This research delves into the anti-inflammatory actions and the associated pathways of nanovesicles originating from human umbilical cord mesenchymal stem cells (UCMSC-NVs) within a model of ALI induced by lipopolysaccharide (LPS). <b>Methods:</b> UCMSC-NVs were prepared via serial extrusion and characterized using transmission electron microscopy and dynamic light scattering. Their effects on pulmonary inflammation and injury were evaluated in an LPS-induced ALI mouse model. Anti-inflammatory effects were analyzed using Western blot, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence, focusing on the role of hsa-let-7g-5p in regulating the nuclear factor κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) pathway. <b>Results:</b> The UCMSC-NVs acquired through serial extrusion displayed bilayer vesicle structures, with a mean diameter of around 100 nm. Moreover, these vesicles exhibited elevated expression levels of CD9, CD63, and CD81. Administration of UCMSC-NVs significantly alleviated lung damage, accompanied by a reduction in alveolar leakage and neutrophil infiltration. Furthermore, it significantly downregulated the expression of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α). UCMSC-NVs reduced macrophage infiltration in the lungs of ALI mice by inhibiting the NF-κB/NLRP3 signaling, leading to a shift in macrophage polarization, with decreased M1 and increased M2 polarization. Our findings demonstrated a novel therapeutic mechanism wherein hsa-let-7g-5p encapsulated within UCMSC-NVs alleviates inflammation by inhibiting NF-κB/NLRP3 expression, thereby mitigating ALI. <b>Conclusion:</b> These results provide a foundation for the development of novel cell-free therapies with clinical potential for treating inflammatory lung diseases such as ALI and acute respiratory distress syndrome (ARDS).</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 2","pages":"465-489"},"PeriodicalIF":8.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking delivery routes: oral administration of plant-derived exosome-like nanovesicles reduces the toxicity of intravenous injection.","authors":"Li Chen, Bo Xiao","doi":"10.20517/evcna.2025.164","DOIUrl":"10.20517/evcna.2025.164","url":null,"abstract":"<p><p>Plant-derived exosome-like nanovesicles (PELNs), as an emerging \"green\" nanoplatform, exhibit broad pharmacological activities, low immunogenicity, and inherent advantages as natural drug carriers. They show great potential in the pharmaceutical, cosmetic, and health supplement sectors. The clinical application of PELNs is heavily contingent on their safety profile, which is intricately linked to the administration route. This opinion compares the safety implications of the two primary routes: oral administration versus intravenous injection. Current evidence indicates that intravenous administration of PELNs triggers complement activation, immune responses, and hepatorenal toxicity; even surface engineering modifications cannot completely eliminate these risks. In contrast, oral administration of PELNs may achieve superior safety by leveraging the gastrointestinal tract's ability to effectively reduce the immunogenic components. Based on these findings, we advocate for the prioritization of oral delivery in the future development of PELNs, given its superior safety profile for realizing their potential as natural therapeutics and drug delivery systems.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"441-447"},"PeriodicalIF":8.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}