Journal of Nanobiotechnology最新文献

{"title":"Synergistic fluvastatin-nanotherapy suppresses DEPDC1-associated glycolysis and exosomal CCL2 to modulate the immune microenvironment in lung adenocarcinoma.","authors":"Chunhua Li, Xingyu Lyu, Tianyi Kang, Xianming Zhang, Li Zhou, Yi Wang, Zhuocai Wei, Ying Huang, Changqi Yuan, Ziyue Zhang, Luyao Wei, Kai Li, Ming Dong","doi":"10.1186/s12951-026-04829-w","DOIUrl":"https://doi.org/10.1186/s12951-026-04829-w","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer, is characterized by high incidence, poor prognosis, limited therapeutic efficacy. Glycolysis-high LUAD is associated with aggressive tumor behavior and immunosuppressive tumor microenvironment (TME) that broadly impairs anti-tumor immunity and therapeutic efficacy. Effective strategies targeting this metabolically aggressive phenotype are urgently needed. In this study, we developed a combination strategy that modulates DEPDC1-associated glycolysis by integrating fluvastatin (Fluv) with an integrin αVβ3-targeted photodynamic nanoplatform (cRGD-TPA-DCR-NP, with light irradiation; NPL), termed Fluv + NPL. Integrated multi-omics analyses, together with Western blotting and glycolytic rate (GlycoPER) measurements, demonstrated that Fluv + NPL suppressed DEPDC1-mediated NF-κB signaling, thereby inhibiting PI3K-AKT-mTOR pathway activity and reducing glycolytic metabolism in LUAD cells. Simultaneously, Fluv + NPL downregulated exosomal CCL2 levels and inhibited M2 macrophage polarization. In vivo studies further showed that Fluv + NPL effectively modulated the immune microenvironment of LUAD, as evidenced by enhanced M1 macrophage polarization, increased infiltration of effector T cells, and reduced M2 macrophage abundance, ultimately resulting in significant inhibition of LUAD growth. Collectively, our findings reveal an important role of DEPDC1 in linking glycolytic metabolism to immune regulation and establish Fluv + NPL as a promising therapeutic strategy that simultaneously suppresses glycolysis and enhances antitumor immunity through modulation of DEPDC1. These results provide new insights into glycolytic metabolism-immunity-based combination therapies for LUAD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial transfer via ADSC-EVs reprograms glucose/glutamine metabolism to restore TCA cycle-driven M2 polarization in diabetic wounds.","authors":"Yue Zhang, Fei Han, Yixuan Yuan, Mengyang Li, Linbin Yi, Yujie Xiao, Dongliang Zhang, Zhi Zhang, Yunchuan Wang, Hongtao Wang, Dahai Hu","doi":"10.1186/s12951-026-04846-9","DOIUrl":"10.1186/s12951-026-04846-9","url":null,"abstract":"<p><p>Chronic diabetic wounds are trapped in a persistent inflammatory state, largely due to macrophage failure to transition from pro-inflammatory (M1) to pro-reparative (M2) phenotypes. Here, we show that adipose-derived stem cell extracellular vesicles (ADSC-EVs) deliver functional mitochondria into diabetic wound macrophages, thereby restoring tricarboxylic acid (TCA) cycle-driven M2 polarization. Mechanistically, ADSC-EV-mediated mitochondrial transfer reactivates pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC), increases TCA cycle flux, and suggests enhanced glutamine anaplerosis, as evidenced by ¹³C-glucose isotope tracing. This metabolic rewiring restores oxidative phosphorylation (OXPHOS), elevates oxygen consumption rate (OCR) and suppresses glycolysis. Consequently, ADSC-EV treatment reduces M1 macrophages and increases M2 macrophages, lowers pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, MCP1, p < 0.0001), and upregulates IL-10 in vitro, p < 0.0001). In a diabetic mouse wound model, a single course of ADSC-EVs accelerates wound closure at day 14 (p < 0.05), enhances re-epithelialization and collagen deposition, and reduces local oxidative stress and inflammation. Mitochondria‑depleted Rho-ADSC-EVs show markedly diminished effects, confirming that functional mitochondrial transfer is the primary driver. Our findings establish ADSC-EV-mediated mitochondrial transfer as a central metabolic reprogramming strategy that breaks the inflammatory lock in diabetic wounds and promotes healing.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine, a chondrocyte apoptotic metabolite, delays osteoarthritis by regulating macrophage M2c polarization.","authors":"Jiajia Lu, Hongbiao Sun, Fan Zhang, Guangnan Wang, Xianan Song, Qinling Jiang, Zhibin Zhou, Jun Ma, Qiang Fu, Lei Zhu","doi":"10.1186/s12951-026-04832-1","DOIUrl":"10.1186/s12951-026-04832-1","url":null,"abstract":"<p><strong>Background: </strong>Chondrocyte apoptosis and synovial macrophage polarization represent two key pathological hallmarks of osteoarthritis (OA), but the interplay between them remains largely unknown. This study aimed to investigate the roles and mechanisms of the chondrocyte apoptotic secretome in mediating macrophage polarization during the pathological process of OA.</p><p><strong>Methods: </strong>In vitro cultures of chondrocytes and macrophages, along with an in vivo surgically induced OA mouse model, were used to evaluate the effect of the chondrocyte apoptotic secretome. Untargeted metabolomics, mitochondrial function assessment, and macrophage-specific AMPKα knockout mice were used to identify key metabolites and their regulatory mechanisms. A sustained-release delivery system for spermidine (SPD) was constructed using lipid nanoparticles (LNPs) and sodium hyaluronate.</p><p><strong>Results: </strong>Apoptotic chondrocytes increased the secretion of SPD in the metabolite secretome. SPD acts as a signaling metabolite to increase AMPKα activation in macrophages, which in turn drives increased oxidative phosphorylation (OXPHOS) and improves mitochondrial function, ultimately promoting M2c macrophage polarization during OA. Exogenous supplementation with SPD via a ROS-responsive SH@LNP@SPD hydrogel alleviated OA progression by promoting M2c macrophage polarization in vivo. Furthermore, elevated SPD levels in synovial fluid correlated with milder clinical symptoms and less severe pathological features.</p><p><strong>Conclusions: </strong>Our findings underscore a significant protective role of chondrocyte apoptosis in early OA mediated through the secretion of SPD, which acts on macrophages. Mechanistically, SPD-induced enhancement of AMPKα activation and OXPHOS occurs specifically in macrophages, driving their beneficial M2c polarization. Synovial fluid SPD may hold diagnostic value for early-stage OA and strategies aimed at sustaining SPD levels may represent effective therapeutic approaches for OA.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-infrared-activated CuTA@PDA@PTH nanozymes remodel the osteoarthritic microenvironment for coordinated cartilage protection and subchondral bone repair.","authors":"Zhao Lin, Jiayao Zhang, Mingjuan Zhang, Mukun Xiao, Hanhao Dai, Yibin Su, Haiqi Ding, Dingqiang Chen, Linhai Yang, Jie Xu, Jun Luo, Yunlong Yu","doi":"10.1186/s12951-026-04841-0","DOIUrl":"10.1186/s12951-026-04841-0","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a progressive whole-joint disorder involving cartilage degeneration, oxidative stress, synovial inflammation, and subchondral bone remodeling. Current treatments mainly provide symptomatic relief and rarely restore joint microenvironmental homeostasis. Here, we developed a multifunctional near-infrared (NIR)-responsive CuTA@PDA@PTH nanozyme, termed CPP, for OA therapy. CPP was constructed through copper-tannic acid coordination, polydopamine coating, and PTH 1-34 incorporation, integrating antioxidant catalytic activity, photothermal responsiveness, and peptide-mediated bioactivity. CPP exhibited uniform morphology, good dispersibility, stable photothermal behavior, and broad-spectrum ROS-scavenging activity with SOD-like and CAT-like functions. In vitro, NIR-activated CPP reduced H₂O₂-induced ROS accumulation, lipid peroxidation, mitochondrial dysfunction, and apoptosis in chondrocytes, while promoting proliferation and restoring cartilage matrix homeostasis. CPP-NIR also downregulated inflammatory and catabolic markers, attenuated M1-associated activation, favored an anti-inflammatory M2-like phenotype, and enhanced BMSC migration and osteogenic differentiation under oxidative stress. In a DMM-induced mouse OA model, intra-articular CPP combined with NIR irradiation prolonged joint retention, attenuated cartilage degeneration, reduced osteophyte formation, improved subchondral bone microarchitecture, and alleviated synovial inflammation. These findings support NIR-activated CPP as a multi-axis nanozyme platform for redox, immune, cartilage, and subchondral bone microenvironment regulation in OA.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic field-controlled nanozymes effectively overcome therapeutic limitations in tumor ferroptosis therapy.","authors":"Xin-Yue Hu, Xiao-Yan Tang, Cong Liu, Xiao-Xiao Gong, Shan-Shan Rao, Chun-Yuan Chen, Zhen-Xing Wang, Hui Xie, Hong-Ji Liu","doi":"10.1186/s12951-026-04796-2","DOIUrl":"10.1186/s12951-026-04796-2","url":null,"abstract":"<p><p>Iron oxide nanozymes with intrinsic peroxidase-like activity and excellent biosafety are considered ideal agents for inducing tumor ferroptosis. However, their practical catalytic efficiency is often constrained by an inherent delocalized electronic structure and the restrictive tumor antioxidant microenvironment. Herein, we report a magnetic field-mediated strategy to synthesize ultra-small superparamagnetic manganese-doped iron oxide (USMIO) nanoparticles with precisely tailored multi-enzyme activities (denoted as MUSMIO). The magnetic field in situ generated abundant oxygen vacancies and optimized the Mn/Fe coordination environment, significantly boosting electron transfer and catalytic performance. MUSMIO exhibited robust pH-responsive peroxidase-like activity with a hydroxyl radical yield ∼5.86-fold higher than pure ultra-small superparamagnetic iron oxide (USIO) and ∼2.43-fold higher than USMIO, together with favorable catalase-, glutathione oxidase-, and nicotinamide adenine dinucleotide phosphate oxidase-like activities. This synergistic multi-enzyme cascade efficiently blocked glutathione regeneration, relieved tumor hypoxia, and triggered a sustained hydroxyl radical storm to drive extensive lipid peroxidation and selective ferroptosis in cancer cells, while exhibiting negligible toxicity to normal cells. In a murine breast cancer model, MUSMIO achieved complete tumor regression with no recurrence, and prolonged the median survival time of mice with excellent biosafety. This work provides a generalizable physical-field-assisted route for designing high-performance multi-enzyme mimetic nanozymes for targeted tumor therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding metabolic diseases through bacterial extracellular vesicles: mechanisms, diagnostics, and therapeutics.","authors":"Di Song, Wenhui Mo, Qiaoyu Deng, Yu Zeng, Yujie Zhang, Xiaoyan Ao, Liling Deng, Xiaoze Wang, Xiaoli Fan","doi":"10.1186/s12951-026-04826-z","DOIUrl":"10.1186/s12951-026-04826-z","url":null,"abstract":"<p><p>Metabolic diseases represent a class of chronic conditions characterized by disturbances in energy and material metabolism. These diseases primarily include obesity, metabolic dysfunction-associated steatotic liver disease, atherosclerosis, type 2 diabetes, osteoporosis, and polycystic ovary syndrome. A core pathological feature underlying their development is the mutual reinforcement between chronic low-grade inflammation and metabolic imbalance. The gut microbiota has been highlighted by recent research as a key regulator of host metabolism, while bacterial extracellular vesicles (BEVs) are emerging as critical mediators. BEVs transport bioactive molecules (proteins, lipids, nucleic acids) to facilitate microbiota-host crosstalk without direct contact. Pathogen-derived BEVs often exacerbate metabolic dysfunction via inflammation, while commensal/probiotic BEVs protect against disorders by enhancing intestinal barrier function and regulating immunity. Furthermore, owing to their high stability, easy penetration of biological barriers, and capacity to carry abundant cellular information, BEVs demonstrate broad application prospects as non-invasive diagnostic biomarkers for metabolic diseases and as natural or engineered targeted drug delivery vehicles. This review outlines the mechanisms and progress in the application of gut BEVs in metabolic diseases. It aims to deepen our understanding of host-microbiota interaction networks and support the development of novel intervention strategies for metabolic diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functionalized metal-organic frameworks as smart nanoplatforms: advancing tumor precision therapy through post-synthetic surface tailoring, challenges, and prospects for clinical translation.","authors":"Shiva Velayati, Masoumeh Zahmatkeshan, Fariba Esmaeili, Seyed Mohammad Hosseini, Seyed Mahdi Rezayat, Mahmoud Reza Jaafari, Kazem Mousavizadeh, Gholamreza Taheripak, Moein Adel, Anna Lesniak, Iraj Alipourfard","doi":"10.1186/s12951-026-04757-9","DOIUrl":"10.1186/s12951-026-04757-9","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) have garnered significant attention as versatile nanocarriers for oncological drug delivery, owing to their exceptional porosity, structural tunability, extensive specific surface areas, and favorable drug loading and release kinetics, which collectively enable targeted payload delivery and reduced systemic toxicity. Nevertheless, the clinical promise of unmodified MOFs is severely curtailed by substantial in vivo biological barriers-including rapid bio-clearance, the immunosuppressive and acidic tumor microenvironment (TME), and inefficient cellular internalization-challenges that are ubiquitous across nanomedicine platforms and critically undermine therapeutic outcomes. This review provides a comprehensive examination of post-synthetic modification (PSM) as an indispensable strategy to surmount these obstacles. It systematically categorizes the diverse array of surface modifiers reported to date into natural polymers, synthetic polymers, nonpolymeric small molecules, inorganic materials, and multifunctional hybrid architectures, while elucidating how each class can enhance biocompatibility, colloidal stability, circulation half-life, active targeting, and stimuli-responsive cargo release. Crucially, the review critically appraises the intrinsic trade-offs introduced by surface engineering, including increased hydrodynamic diameter, impaired tumor penetration, heightened synthetic and characterization complexity, and unpredictable perturbations to biodegradation pathways and immune system interactions. Despite robust preclinical validation, the translational trajectory of surface-engineered MOF-based therapeutics remains encumbered by formidable challenges spanning scalable and reproducible manufacturing, long-term biosafety assessment, and stringent regulatory approval. By delineating current advances, critical limitations, and prospective directions, this review highlights the delicate equilibrium between surface functionalization and biological performance that must be achieved to realize the clinical potential of PSM-optimized MOF nanomedicines.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schwann cell-derived extracellular vesicles promote periodontal tissue regeneration.","authors":"Ting Zhang, Jiaying Liu, Xiyue Wang, Yu Wu, Mengjia Wang, Shuyu Cheng, Rong Liu, Shuang Zhang, Yangheng Zhang, Yin Xiao, Yanan Zhu, Fuhua Yan","doi":"10.1186/s12951-026-04848-7","DOIUrl":"10.1186/s12951-026-04848-7","url":null,"abstract":"<p><p>Periodontitis is a common chronic inflammatory disease worldwide, and conventional therapies control inflammation but fail to achieve predictable regeneration. The inferior alveolar nerve (IAN) is a key peripheral nerve that governs mandibular bone homeostasis, and its disruption precipitates bone metabolic imbalance and impaired repair. However, the dynamic behavior of Schwann cells (SCs), the principal glial cells of this neural axis, and their mechanistic influence on periodontal ligament stem cells (PDLSCs) remain elusive. We established a rat IAN transection model and found that denervation induced progressive alveolar bone deterioration and compromised the osteogenic capacity of resident PDLSCs. Correlation analyses revealed that this bone deterioration coincided with progressive SC depletion in periodontal tissue, suggesting a link between Schwann cell loss and PDLSC dysfunction. Transcriptomic profiling of denervated PDLSCs revealed that dysregulated AMPK/mTOR signaling and suppressed autophagy are mechanisms underlying osteogenic impairment. Co-culture with SCs restored PDLSC proliferation and osteogenic differentiation, with SC-derived extracellular vesicles (SC-EVs) as important paracrine mediators of this effect. Mechanistically, SC-EVs delivered rno-miR-210-5p, which targeted the DAP1 gene and suppressed its expression, thereby activating the AMPK/mTOR-autophagy axis and rescuing osteogenic potential. In a rat denervated mandibular defect model, SC-EVs significantly enhanced bone regeneration. Collectively, these findings suggest that Schwann cells and their EVs participate in the neural regulation of periodontal bone metabolism and may play an important role in periodontal regeneration.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived extracellular vesicles deliver spermidine to reprogram macrophage metabolism and ameliorate rheumatoid arthritis.","authors":"Xiaocheng Wang, Jiaxin He, Yixiang Hong, Xingyue Zeng, Min Li, Shixiong Cao, Renge Liang, Gengmin Zhou, Qingwen Wang","doi":"10.1186/s12951-026-04836-x","DOIUrl":"10.1186/s12951-026-04836-x","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is driven by macrophage-mediated synovial inflammation closely linked to metabolic dysfunction, highlighting immunometabolism as a therapeutic target. Here, we engineered spermidine-loaded red cabbage-derived extracellular vesicles (RCEVs@SPD) as a plant-based nanoplatform to reprogram macrophage bioenergetics. In LPS-stimulated macrophages, RCEVs@SPD suppressed pro-inflammatory polarization and enhanced mitochondrial function, as evidenced by increased ATP production and mitochondrial membrane potential. Assay-based measurements further showed reduced extracellular acidification rate (ECAR) and elevated oxygen consumption rate (OCR), indicating a shift from glycolysis toward oxidative phosphorylation (OXPHOS). Untargeted LC-MS metabolomics revealed coordinated alterations in pathways supporting mitochondrial cofactor biosynthesis, redox balance, and central carbon metabolism. Transcriptomic analysis confirmed enrichment of OXPHOS and mitochondrial respiration gene signatures with concomitant repression of glycolytic programs and PI3K-AKT signaling. In vivo, RCEVs@SPD significantly alleviated collagen-induced arthritis, improved joint histopathology, and promoted anti‑inflammatory macrophage polarization. Notably, systemic macrophage depletion abolished the additional therapeutic benefit of RCEVs@SPD, demonstrating macrophage dependence. Collectively, these findings establish plant-derived extracellular vesicles as a biocompatible delivery system that potentiates spermidine to restore macrophage metabolic balance and mitigate RA pathology.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactobacillus mucosae extracellular vesicles improve metabolic dysfunction-associated fatty liver disease by activating the AMPK pathway via the gut-liver axis.","authors":"Kaige Zhang, Yuyu Zeng, Zhaohui Liao, Jianhua Wu, Xilong Zhang, Tingtao Chen, Zhengyuan Xie","doi":"10.1186/s12951-026-04843-y","DOIUrl":"10.1186/s12951-026-04843-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide but lacks effective therapies. Gut microbiota play a key role in MAFLD via the gut-liver axis, yet targeted interventions remain unclear. This study investigates the therapeutic effects and mechanisms of Lactobacillus mucosae (L. mucosae) and its extracellular vesicles (EVs) in MAFLD.</p><p><strong>Methods: </strong>At the clinical level, 16S rRNA sequencing was performed to analyze differences in gut microbiota composition between MAFLD patients and healthy controls, followed by the identification of a core probiotic strain, L. mucosae, using culture-based approaches. A high-fat diet-induced MAFLD mouse model was subsequently established to evaluate the therapeutic effects of L. mucosae, while free fatty acid-induced hepatocyte models were used to identify L. mucosae-EVs as the key active component. Mechanistic investigations and validation were further conducted in vivo and in vitro using RNA sequencing, qPCR, Western blot analyses, DIA-based EV proteomics, and Proteinase K-mediated EV protein functional assays.</p><p><strong>Results: </strong>MAFLD patients showed reduced intestinal Lactobacillus abundance, negatively correlated with hepatic lipid parameters. L. mucosae administration alleviated steatosis, metabolic dysfunction, inflammation, and oxidative stress in mice. In vitro, L. mucosae-EVs were confirmed as the main active component, and Proteinase K-pretreated EVs showed attenuated protective effects on hepatocytes. Mechanistically, L. mucosae-EVs activated hepatic AMPK signaling via the gut-liver axis, remodeled gut microbiota, and restored intestinal barrier integrity.</p><p><strong>Conclusion: </strong>This study systematically demonstrates for the first time that L. mucosae-EVs ameliorate MAFLD through multiple mechanisms, including gut microbiota remodeling, intestinal barrier restoration, and activation of hepatic AMPK signaling via the gut-liver axis. Proteinase K-mediated functional assays suggest that EV-associated protein cargo contributes, at least in part, to these protective effects. These findings provide a solid experimental foundation and theoretical basis for the development of precision microbiome-based therapeutic strategies for MAFLD based on L. mucosae and its EVs.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}