Molecular biomedicine最新文献

{"title":"Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities.","authors":"Wei Cheng, Haotian Cao, Hao Hu, Rui Qian, Bingjie Xu, Jing Zhang","doi":"10.1186/s43556-026-00586-2","DOIUrl":"10.1186/s43556-026-00586-2","url":null,"abstract":"<p><p>Pancreatic cancer is one of the most lethal digestive system malignancies worldwide, characterized by insidious onset, limited early detection approaches and extremely poor long-term prognosis. It comprises multiple histological subtypes, among which pancreatic ductal adenocarcinoma (PDAC) represents the most prevalent exocrine neoplasm and accounts for the vast majority of all pancreatic cancer cases. Perineural invasion (PNI) stands as one of the defining biological hallmarks of PDAC. Detected in 80%-100% of PDAC patients, PNI serves as an independent adverse prognostic factor that drives local recurrence, distant metastasis, and resistance to both chemotherapy and immunotherapy. Historically regarded as a passive route for tumor dissemination, PNI is now recognized as a complex, multicellular process involving bidirectional crosstalk between cancer cells, nerve fibers, stromal cells, and immune components within the tumor microenvironment. This review dissects the molecular mechanisms underlying neuro-tumor interactions and proposes a unified four-stage mechanistic model of PNI, encompassing mutual chemotaxis between tumors and nerves, adhesion and invasion at the tumor-nerve interface, extracellular matrix remodeling, and neural plasticity alterations. Notably, we define the perineural invasion microenvironment as a neuro-immune privileged sanctuary, and delineate its multicellular composition and pathological consequences based on current research advances. Furthermore, we summarize potential therapeutic strategies targeting the neuro-immune-tumor axis and ongoing clinical trials, discuss key translational challenges, and highlight the transformative applications of multi-omics technologies and artificial intelligence in PNI diagnosis, mechanistic discovery, and therapeutic optimization. This work provides a comprehensive theoretical framework for understanding PNI mechanisms and guides future translational research and precision therapy development for pancreatic cancer.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984201","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":"Nasopharyngeal carcinoma: epidemiology, risk factors, signaling pathways, clinical features, diagnosis, and management.","authors":"Yangbingyu Wen, Yue Xu, Yao Du, Yuting Zhan, Songqing Fan","doi":"10.1186/s43556-026-00590-6","DOIUrl":"10.1186/s43556-026-00590-6","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is a distinctive epithelial malignancy characterized by marked geographic and ethnic clustering, with the greatest burden concentrated in East and Southeast Asia despite declining age-standardized incidence and mortality rates in many regions. NPC arises from a complex interaction among persistent Epstein-Barr virus (EBV) infection, inherited susceptibility, and environmental exposures. Among these factors, EBV plays a central role in endemic NPC through latent gene products, particularly latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), and Epstein-Barr nuclear antigen 1 (EBNA1), which sustain oncogenic signaling, remodel the tumor microenvironment, and reinforce malignant progression. Clinically, NPC is often diagnosed at a locoregionally advanced stage because of its deep anatomical location and nonspecific early symptoms, making accurate detection, risk stratification, and treatment selection particularly important. Although previous reviews have addressed individual aspects of NPC biology or management, an integrated framework linking epidemiological determinants, viral oncogenesis, host molecular dysregulation, and therapeutic evolution remains needed. This review therefore synthesizes current evidence on NPC epidemiology, risk factors, EBV-associated molecular mechanisms, major signaling pathways and their crosstalk, genetic and epigenetic alterations, clinical features, diagnosis, staging, and management. Particular emphasis is placed on the clinical roles and limitations of plasma EBV DNA, the distinction between established standards and investigational strategies, and emerging molecular and immune-based therapies. By linking mechanistic insights with their clinical and translational implications, this review provides a biologically informed framework for understanding NPC and highlights priorities for biomarker standardization, risk-adapted treatment, and future therapeutic development.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992965","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":"Transcriptome-based epigenetic screening identifies DNA hypermethylation signatures as prognostic biomarkers in oral squamous cell carcinoma.","authors":"Yu Kyeong Han, Jihye Park, Hye Su Han, Keunsoo Kang, Hae Ryoun Park, Joo Mi Yi","doi":"10.1186/s43556-026-00584-4","DOIUrl":"10.1186/s43556-026-00584-4","url":null,"abstract":"<p><p>Promoter DNA hypermethylation is a key epigenetic mechanism of gene silencing in cancer, yet the DNA hypermethylome of oral squamous cell carcinoma (OSCC) and its prognostic relevance remain poorly characterized. Here, we systematically identified and validated novel hypermethylated genes with prognostic significance in OSCC using a genome-wide discovery and multi-platform validation strategy. Candidate genes were first identified by pharmacologic demethylation combined with RNA sequencing across OSCC cell lines, then validated by quantitative RT-PCR, methylation-specific PCR, and bisulfite sequencing in OSCC cell lines, normal oral mucosa, and primary OSCC tumors, with independent confirmation in the TCGA-HNSC dataset. Immunohistochemistry confirmed protein-level silencing, and Kaplan-Meier survival analysis assessed prognostic significance across both cohorts. This pipeline identified five candidate genes, GPX3, ANG, CTGF, GPRC5B, and BAMBI, exhibiting cancer-specific promoter hypermethylation associated with transcriptional and protein silencing in OSCC. Validation in oral cavity tumor samples extracted from the TCGA-HNSC dataset confirmed tumor-specific hypermethylation and revealed significant inverse correlations between methylation and expression for GPX3, GPRC5B, and CTGF. Notably, CTGF hypermethylation was independently associated with poor overall survival in both cohorts (institutional cohort, p=0.03; oral tumor subset from TCGA-HNSC, p=0.01), and a combined ANG+CTGF methylation signature showed superior and reproducible prognostic performance across both platforms. Pathway analysis linked these genes to epithelial-mesenchymal transition and interferon response signaling. This study establishes the first validated DNA methylation biomarker panel for OSCC prognosis, identifying CTGF hypermethylation as a robust prognostic driver with translational potential for clinical risk stratification.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984194","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 in targeted drug delivery: from biological functions to surface engineering.","authors":"Giulia Duca, Vincenza Tinnirello, Nima Rabienezhad Ganji, Riccardo Alessandro, Stefania Raimondo","doi":"10.1186/s43556-026-00578-2","DOIUrl":"10.1186/s43556-026-00578-2","url":null,"abstract":"<p><p>Achieving precise and efficient targeting represents a major challenge in drug delivery to overcome the limitations of conventional therapies. Surface functionalization of extracellular vesicles (EVs)-nanosized membranous particles released by all cell types- has emerged as a promising strategy to enhance targeted drug delivery. EVs are naturally involved in intercellular communication by transferring bioactive molecules from donor to recipient cells, and their biologically active interface confers inherent targeting properties and a favorable safety profile, making them attractive vehicles compared to synthetic nanoparticles. However, the naїve use of EVs is often limited by nonspecific biodistribution and off-target accumulation, reducing their therapeutic efficacy. To overcome these limitations, increasing efforts have focused on engineering EVs through cargo loading and surface functionalization strategies, enabling enhanced targeting and improved delivery of therapeutic molecules. In this review, we first describe the biological features of EVs, including their biogenesis, heterogeneity, and molecular composition, which underlie their potential as drug delivery systems. We then discuss the main determinants of EV-mediated drug delivery and present current engineering strategies, including cargo loading and surface functionalization approaches, highlighting their advantages and limitations. Finally, we summarize the application of engineered EVs in the treatment of several pathological conditions, including cardiovascular, neurological, autoimmune, and cancer diseases, and discuss the major challenges in clinical translation and future perspectives for EV-based targeted therapies.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984261","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":"Cardiac fibrosis: mechanistic insights and translational advances.","authors":"Hui-Yi Xie, Xue-Ting Zheng, Xiu-Heng Wang, Jia-Yan Yang, Yun-Xi Liu, Yue Zhao, Hui-Fang Tang, Heng-Jing Hu","doi":"10.1186/s43556-026-00587-1","DOIUrl":"10.1186/s43556-026-00587-1","url":null,"abstract":"<p><p>Cardiac fibrosis is a critical pathological process driving the progression of heart failure, characterized by excessive extracellular matrix deposition, collagen network remodeling, and expansion of the myocardial interstitium. While fibrosis may reflect a reparative response to tissue injury, it can also signify a maladaptive remodeling process that progressively impairs cardiac structure and function. Cardiac fibroblasts and myofibroblasts serve as the principal effector cells responsible for matrix accumulation, whereas cardiomyocytes and immune cells contribute to fibrotic expansion through inflammatory signaling, paracrine communication, and microenvironmental regulation. Transforming growth factor-β, the renin-angiotensin-aldosterone system, inflammatory cytokines, mechanical stress, and metabolic disturbances collectively orchestrate a profibrotic signaling network. By regulating extracellular matrix synthesis, degradation, and crosslinking, these pathways promote myocardial stiffening and functional decompensation. In this review, we discuss the histopathological patterns of cardiac fibrosis across various pathological contexts, the major cellular contributors, and the core molecular mechanisms involved, while summarizing current advances in diagnostic evaluation and translational therapeutic strategies. We further discuss the context-dependent role of sirtuin 3 (SIRT3), a mitochondrial nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, in linking mitochondrial homeostasis, oxidative stress, metabolic adaptation, and profibrotic signaling. More precise antifibrotic strategies require better definition of fibroblast states, fibrosis activity, and disease-specific remodeling patterns.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984225","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":"Betaine-driven Keap1 methylation promotes p62-mediated autophagy and Nrf2 stabilization to alleviate glutathione-dependent redox dyshomeostasis in liver injury.","authors":"Moon Han Chang, Chae Hwan Lee, Yeongrae Cho, Ryeo Gang Son, Seoyoon Lee, Shinwoo Park, Jaeryeong Kim, Young Ho Koh, Art E Cho, Seung Pil Pack, Minseok Seo, Jin Hyup Lee, Hanvit Cha","doi":"10.1186/s43556-026-00579-1","DOIUrl":"10.1186/s43556-026-00579-1","url":null,"abstract":"<p><p>Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates detoxification and antioxidant programs that protect the liver from chemical and metabolic stress. Nrf2 is restrained by Kelch-like ECH-associated protein 1 (Keap1), which can be removed through p62-mediated selective autophagy; however, nutritional cues that engage this pathway remain incompletely understood. This study provides evidence that betaine (trimethylglycine; BET) can regulate the Keap1-Nrf2 axis through modulation of Keap1. In biochemical and cellular assays, betaine was associated with methylation of Keap1 at Cys513 and Cys518 within the Kelch domain, which was linked to enhanced p62-dependent autophagic degradation of Keap1 and Nrf2 stabilization. In AML12 hepatocytes and in mice, betaine enhanced Nrf2 activity, induced canonical Nrf2 target genes, and increased cellular glutathione (GSH), consistent with improved GSH-dependent redox capacity. In an acetaminophen (AAP) overdose model, betaine attenuated hepatic injury, consistent with improved redox capacity under acute toxic stress. In an MCD diet-induced steatotic liver disease model, betaine was associated with reduced steatohepatitis-like histopathology, inflammatory signaling, and lipogenic markers. Finally, RNA-seq analysis of a large human metabolic dysfunction-associated steatotic liver disease (MASLD) cohort revealed Nrf2-related transcriptomic signatures associated with disease severity, providing correlative support for the disease relevance of this pathway. Collectively, these findings suggest that Keap1 cysteine methylation may represent a regulatory node linking betaine to p62-mediated autophagy, Nrf2 stabilization, and GSH homeostasis, while further studies are required to establish the causal and translational relevance of this mechanism in human liver disease.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984231","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":"¹⁷⁷Lu-trastuzumab radionuclide therapy: a promising strategy for trastuzumab-resistant brain metastases in HER2+ breast cancer.","authors":"Liliana Santos, Ivanna Hrynchak, José Sereno, Hugo R S Ferreira, Magda Silva, Alexandra Fonseca, Rui Almeida, Paulo Teixeira, Antero J Abrunhosa, Célia M F Gomes","doi":"10.1186/s43556-026-00573-7","DOIUrl":"10.1186/s43556-026-00573-7","url":null,"abstract":"<p><p>Brain metastases (BrM) are a frequent and devastating complication of HER2-positive (HER2+) breast cancer (BC), affecting up to 30% of patients with metastatic disease. Although trastuzumab has transformed HER2+ BC treatment, its efficacy against BrM remains limited by brain-specific resistance mechanisms and heterogeneous blood-brain barrier (BBB) permeability. Here, we investigated whether HER2-targeted radionuclide therapy (TRT) using the β-emitting radioimmunoconjugate [¹⁷⁷Lu]Lu-DOTA-trastuzumab could overcome trastuzumab resistance in HER2+ brain metastatic lesions. Brain-tropic cells retained HER2 expression but showed reduced sensitivity to trastuzumab, indicating the emergence of resistance mechanisms independent of target loss. By contrast, treatment with [¹⁷⁷Lu]Lu-DOTA-trastuzumab produced robust DNA double-strand break-mediated cytotoxicity irrespective of trastuzumab sensitivity, demonstrating that resistance to antibody-mediated signaling inhibition does not confer cross-resistance to radiation-induced cell killing. In vivo, a single dose of [¹⁷⁷Lu]Lu-DOTA-trastuzumab markedly reduced tumor progression and led to complete remission of established BrM in 40% of treated animals, whereas unconjugated trastuzumab showed minimal therapeutic benefit. Importantly, treatment was not associated with detectable neurotoxicity. While dynamic contrast-enhanced MRI demonstrated widespread BBB disruption across metastatic lesions, [⁸⁹Zr]Zr-DFO-trastuzumab PET revealed marked heterogeneity in intracranial antibody delivery, with tracer uptake restricted to a subset of lesions. Collectively, these findings demonstrate that HER2-TRT can overcome trastuzumab resistance and eradicate brain metastatic lesions. Moreover, immuno-PET provides a non-invasive biomarker of intracranial antibody accessibility, supporting a theranostic strategy that combines patient stratification with TRT for HER2+ BrM.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972783","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":"HDCA suppresses exosomal lncRNA MSTRG171708 release to inhibit Treg-mediated immunometabolism in hepatocellular carcinoma.","authors":"Feng Yang, Wenqiong Huang, Chongkai Fang, Chong Zhong, Chaoyuan Huang, Meijun Liu, Zongzhen Meng, Xiaoli Chen, Claudio Mauro, Aiping Lyu, Kenneth C P Cheung","doi":"10.1186/s43556-026-00550-0","DOIUrl":"10.1186/s43556-026-00550-0","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) exhibits poor patient outcomes due to its propensity for metastasis, yet the mechanisms linking metabolic dysregulation and immune evasion remain unclear. This study reveals that reduced hyodeoxycholic acid (HDCA) levels, coupled with elevated tumor-derived extracellular vesicles (EVs) carrying the long non-coding RNA MSTRG171708, correlate with aggressive HCC progression and enhanced lung metastasis. Mechanistically, MSTRG171708-enriched EVs are internalized by regulatory T (Treg) cells, stabilizing the HIF-1α/PKM2/PHD3 axis and triggering a metabolic shift toward glycolysis, thereby augmenting Treg migratory capacity and fostering an immunosuppressive microenvironment conducive to metastasis. Furthermore, HDCA suppresses EVs release by transcriptionally downregulating RAB27 and SNAP23, key mediators of exosome biogenesis, and effectively curtails metastatic burden in vivo. Clinically, high MSTRG171708 levels in HCC patients are associated with decreased HDCA levels and increased Treg infiltration. These findings establish HDCA-mediated regulation of EVs trafficking as a critical link between epigenetic modulation and immunometabolic reprogramming, proposing HDCA restoration as a novel therapeutic strategy to impede HCC metastasis.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946285","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":"Neuroimmune interactions: from molecular mechanisms to therapeutic targets.","authors":"Yi-Hang Hao, Rong-Jia Shi, Ya-Ling Tang, Xin-Hua Liang","doi":"10.1186/s43556-026-00565-7","DOIUrl":"10.1186/s43556-026-00565-7","url":null,"abstract":"<p><p>Neuroimmune interactions reveal that the central nervous system (CNS) is dynamically integrated with peripheral immunity. This bidirectional communication is mediated by microglia, astrocytes, peripheral immune cells, and the neurovascular unit through cytokines, chemokines, complement proteins, neurotransmitters, and neuropeptides. At the molecular level, pattern-recognition receptors, including Toll-like receptors and nucleotide-binding oligomerization domain-like receptors, activate NF-κB, MAPK, and JAK-STAT signaling. These pathways regulate cytokine production, oxidative stress, cellular metabolism, and glial phenotypes. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation induces caspase-1-dependent maturation of IL-1β and IL-18 and promotes pyroptosis, thereby amplifying neuroinflammation. Complement C1q/C3-CR3 signaling mediates synaptic pruning, whereas C-C motif chemokine ligand 2 (CCL2)-CCR2 signaling promotes leukocyte recruitment and microglial activation. Cytokines and matrix metalloproteinases disrupt endothelial tight junctions and compromise blood-brain barrier integrity. In addition, calcitonin gene-related peptide (CGRP) and substance P activate neuropeptide receptors to drive neurogenic inflammation. Together, these molecular circuits regulate glial activation, immune-cell trafficking, synaptic remodeling, neuronal excitability, vascular function, and cell survival. Their dysregulation contributes to neurodegenerative, neuroinflammatory, psychiatric, neurodevelopmental, and peripheral diseases through the blood-brain barrier, gut-brain axis, and vagus nerve. This Review summarizes how molecular neuroimmune mechanisms drive disease initiation, progression, and heterogeneity, and discusses emerging therapies targeting inflammasomes, complement, chemokine receptors, neuropeptide signaling, and microbiota to advance biomarker-guided, personalized neuroimmune medicine.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922190","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 for next-gen therapeutics and drug delivery.","authors":"Nawaz Khan, Zeynab Ahmadova, Yujie Shi, Tayyab Shafiq, Yujie Liang, Li Duan","doi":"10.1186/s43556-026-00571-9","DOIUrl":"10.1186/s43556-026-00571-9","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are membrane-bound, nano-sized particles released by diverse cell types. They serve as key mediators of intercellular communication by transporting a broad repertoire of proteins, lipids, nucleic acids, and metabolites to recipient cells within a protective lipid bilayer. Owing to their natural origin, intrinsic stability, low immunogenicity, and ability to cross biological barriers, EVs are highly attractive candidates for next-generation therapeutics and drug delivery platforms. In this review, we summarize the biology of EVs and highlight the features critical for their application in therapeutic delivery. We trace their multiple origins, ranging from mammalian and plant cells to bacteria, underscoring their ubiquity across biological systems. We then analyze the advantages of EVs as next-generation delivery vehicles. From a practical standpoint, we examine current strategies for EV isolation, purification, characterization, and engineering. Importantly, we showcase several therapeutic applications of EVs for intractable diseases that are refractory to conventional approaches, such as cancer and immune disorders. We also discuss the major challenges on the path to clinical translation, particularly scalable and standardized production, as well as safety and immunogenicity. To fully realize the clinical potential of EV-based therapies, future research should prioritize the development of robust manufacturing protocols and comprehensive safety evaluations.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"7 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914579","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}