Journal of Nanobiotechnology最新文献

{"title":"Ligustrazine nano-drug delivery system ameliorates doxorubicin-mediated myocardial injury via piezo-type mechanosensitive ion channel component 1-prohibitin 2-mediated mitochondrial quality surveillance.","authors":"Junyan Wang, Haowen Zhuang, Chun Li, Ruiqi Cai, Hongshuo Shi, Boxian Pang, Zhijiang Guo, Sang-Bing Ong, Yifeng Nie, Yingzhen Du, Hao Zhou, Xing Chang","doi":"10.1186/s12951-025-03420-z","DOIUrl":"10.1186/s12951-025-03420-z","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) demonstrates significant therapeutic and anticancer efficacy. Nevertheless, it demonstrates significant cardiotoxicity, resulting in permanent cardiac damage. Ligustrazine (LIG) is a bioactive alkaloid derived from the rhizome of the medicinal plant Ligusticum chuanxiong Hort. The alkaloid has exhibited cardioprotective properties. The therapeutic application of LIG is constrained by inadequate water solubility, fast breakdown, and low bioavailability. Nanoparticle drug delivery technologies effectively address these constraints by encapsulating LIG into nanocarriers, significantly enhancing its solubility and bioavailability, hence maximizing its therapeutic efficacy. Consequently, this study employed tetrahedral backbone nucleic acid molecules as LIG carriers. Furthermore, animal models and single-cell sequencing analyses were employed to forecast the mechanisms and targets of pertinent studies. A mouse model genetically modified for the piezo type mechanosensitive ion channel component 1 (PIEZO1), transmembrane BAX inhibitor motif containing 6 (TMBIM6), and prohibitin 2 (PHB2), along with an in vivo and in vitro model of DOX-induced cardiomyopathy (DIC), was established, and a gene-modified cellular system comprising upstream genes and downstream effector targets was constructed. The mechanism of LIG was validated by molecular biology and integrated pharmacology with the implementation of the LIG nano-drug loading method.</p><p><strong>Results: </strong>LIG nano-delivery enhanced DOX-induced cardiac dysfunction and mitochondrial impairment by modulating the PHB2Ser91/Ser176 phosphorylation axis through PIEZO1-TMBIM6, and significantly suppressed cardiomyocyte pyroptosis resulting from mitochondrial homeostasis dysregulation. The findings indicate that LIG nano-delivery is a promising therapeutic approach for addressing DIC.</p><p><strong>Conclusion: </strong>The PHB2Ser91/Ser176 phosphorylation axis regulated by PIEZO1-TMBIM6 is an important target for LIG nano-drug delivery systems to improve mitochondrial damage in DIC.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"383"},"PeriodicalIF":10.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159654","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":"Nanoparticle-mediated SIRT1 inhibition suppresses M2 macrophage polarization and hepatocarcinogenesis in chronic hepatitis B.","authors":"He Zhang, Feng Yuan, Nan Zhao, Wenqiang Tang, Pengwei Zhao, Chunfa Liu, Shan Chen, Xiaolin Hou, Changyou Xia, Jun Chu","doi":"10.1186/s12951-025-03447-2","DOIUrl":"10.1186/s12951-025-03447-2","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis B (CHB), with macrophage M2 polarization playing a critical role in shaping the tumor-promoting hepatic immune microenvironment. Sirtuin 1 (SIRT1) has been implicated in immune modulation and liver carcinogenesis. This study investigates the potential of Mimetic Nanoparticles (MNPs) for delivering SIRT1 inhibitors to regulate macrophage polarization and remodel the hepatic immune microenvironment, aiming to prevent HCC development post-CHB. A transgenic mouse model of CHB was established, and RNA sequencing (RNA-seq) and proteomics analyses revealed significant dysregulation of genes associated with M2 macrophage polarization, particularly SIRT1. Functional enrichment analysis highlighted key pathways, including PI3K-Akt and NF-κB, that contribute to CHB-driven immune alterations. Synthesized and characterized MNPs successfully delivered SIRT1 inhibitors, effectively inhibiting M2 macrophage polarization in vitro. In vivo administration of MNPs-SIRT1-FN significantly reduced M2 macrophage infiltration and suppressed tumor growth. These findings suggest that nanoparticle-mediated SIRT1 inhibition is a promising strategy for immunomodulation and HCC prevention in CHB patients. This study provides novel insights into nanoparticle-based immunotherapy for CHB-related HCC and highlights a potential therapeutic avenue for liver cancer prevention.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"385"},"PeriodicalIF":10.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159656","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":"Sequential nanoparticle therapy targeting neutrophil hyperactivation to prevent neutrophil-induced pulmonary fibrosis.","authors":"Hye-Jin Lee, Na Kyeong Lee, Jisun Kim, Jungbum Kim, Donghyuk Seo, Ha Eun Shin, Jongsu Kim, June Hong Ahn, Se-Na Kim, Hong Sook Kim, Juwon Park, Wooram Park, Kyung Soo Hong, Chun Gwon Park, Wonhwa Lee","doi":"10.1186/s12951-025-03421-y","DOIUrl":"10.1186/s12951-025-03421-y","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis, a major complication of severe COVID-19 and post-acute sequelae of SARS-CoV-2 infection (PASC), is driven by excessive neutrophil activation and the formation of neutrophil extracellular trap (NET).</p><p><strong>Results: </strong>This study presents a sequential nanoparticle-based therapy combining DNase-I-loaded polydopamine nanoparticles (DNase-I@PDA NPs) with Sivelestat-encapsulated PLGA nanoparticles (Siv@PLGA NPs) to target both NETs and neutrophil elastase (NE) activity. DNase-I@PDA NPs were aerosolized to the lungs, facilitating NET clearance and reducing the fibrotic microenvironment, followed by intravenous administration of Siv@PLGA NPs to inhibit NE activity and prevent neutrophil hyperactivation. In a murine model of lipopolysaccharide (LPS)-induced pulmonary fibrosis, this dual approach significantly decreased fibrotic lesions, collagen deposition, and myofibroblast activation. Notably, treatment with the nanoparticles led to substantial improvements in pulmonary function. In neutrophils isolated from COVID-19 patients, the combined nanoparticle therapy reduced circulating cell-free DNA, NET, NE, and myeloperoxidase (MPO) levels, while enhancing neutrophil viability and reducing inflammatory responses.</p><p><strong>Conclusions: </strong>These findings highlight the efficacy of DNase-I@PDA NPs and Siv@PLGA NPs in addressing both acute inflammation and chronic fibrosis by simultaneously targeting NET formation and neutrophil hyperactivation. This dual nanoparticle therapy represents a promising clinical strategy for treating COVID-19-associated pulmonary complications, including PASC, by preventing long-term fibrotic progression and promoting lung recovery.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"381"},"PeriodicalIF":10.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150747","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":"Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood-brain barrier permeability.","authors":"Suyi Liu, Xingyue Jin, Yuanyuan Ge, Junlin Dong, Xinyue Liu, Xiao Pei, Ping Wang, Bing Wang, Yanxu Chang, Xie-An Yu","doi":"10.1186/s12951-025-03415-w","DOIUrl":"10.1186/s12951-025-03415-w","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) represents a formidable challenge in the treatment of neurological disorders, as it restricts the passage of most therapeutic agents into the central nervous system (CNS). Research in brain-targeted delivery strategies and explore in natural products for BBB modulation have opened new avenues for effective CNS drug delivery. This review highlights the latest developments in molecular-based delivery systems, cell-based approaches, physical techniques, toxicity concerns, clinical trials and artificial intelligence (AI) -driven modeling for brain-targeted drug delivery. Additionally, it examines the role of natural products, particularly aromatic resuscitation medicines, in enhancing BBB permeability through modulating tight junction proteins and inhibiting efflux transporters. It is emphasized that the integration of natural products with modern drug delivery systems offers promising opportunities for the development of novel brain-targeted therapies. However, challenges related to the complexity and variety of natural product compositions must be addressed to fully realize their potential. This review underscores the importance of continued research into the molecular mechanisms underlying BBB modulation and natural product-mediated nano-delivery strategies for CNS disorders.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"382"},"PeriodicalIF":10.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150742","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":"Multifunctional hydrogel with mild photothermal properties enhances diabetic wound repair by targeting MRSA energy metabolism.","authors":"Qian Gao, Fangfang Hu, Zihan Chai, Caiyun Zheng, Wenhui Zhang, Ke Pu, Ziyi Yang, Yanni Zhang, Seeram Ramrkrishna, Xianglong Wu, Tingli Lu","doi":"10.1186/s12951-025-03451-6","DOIUrl":"10.1186/s12951-025-03451-6","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wound infections, exacerbated by multidrug-resistant pathogens like MRSA, remain a critical challenge due to biofilm persistence and dysregulated oxidative-inflammatory-metabolic crosstalk.</p><p><strong>Results: </strong>In this work, we engineered COG-Z@P200 hydrogel, a chitosan-based hydrogel integrating polydopamine-coated ZIF-8 nanoparticles, to synergize mild photothermal therapy (40-45 °C) with metabolic-immune reprogramming. Upon NIR irradiation, COG-Z@P200 disrupted MRSA through Zn²⁺-mediated membrane destabilization and localized hyperthermia, achieving >99.5% eradication via combined physical puncture and metabolic interference. Multi-omics analyses revealed suppression of glycolysis (eno, gap downregulation), TCA cycle arrested (sucC, sdhA, icd inhibition), and disruption of arginine biosynthesis (arcA, arcC, arcD downregulation), impairing biofilm formation and pathogenicity. Concurrent silencing of quorum sensing and virulence genes (agr, sec, lac, opp, sdrD) further destabilized MRSA, while upregulation of stress-response genes (yidD, nfsA, kdpA) indicated bacterial metabolic paralysis. In diabetic murine models, the hydrogel attenuated oxidative stress (DHE-confirmed ROS reduction), polarized macrophages to pro-healing M2 phenotypes (Arg-1⁺/TNF-α↓), and enhanced angiogenesis (VEGF/CD31↑) alongside aligned collagen deposition. This multifunctional action accelerated wound closure by 48% versus controls, outperforming clinical standards. By converging nanomaterial-enabled bactericidal strategies with host microenvironment recalibration, COG-Z@P200 hydrogel redefined diabetic wound management, offering an antibiotic-free solution against multidrug-resistant infections.</p><p><strong>Conclusion: </strong>Our work established a biomaterial paradigm that concurrently targets pathogen vulnerabilities and restores tissue homeostasis, addressing the multidimensional complexity of chronic wounds.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"380"},"PeriodicalIF":10.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150745","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":"A lyophilizable LNP vaccine enables STING-reinforced postoperational adjuvant immunotherapy.","authors":"Yi Yang, Jiaxin Guo, Jialong Qi, Wenxia Deng, Jialin Hu, Muhammad Waqqas Hasan, Fei Deng, You Zhou, Zhengji Song, Wei Deng, Wenjie Chen","doi":"10.1186/s12951-025-03445-4","DOIUrl":"10.1186/s12951-025-03445-4","url":null,"abstract":"<p><p>Immune checkpoint blockade therapy (iCBT) has revolutionized cancer treatment, however, there is a low response rate, especially in treating postsurgical reoccurring tumors. Vaccine based immunotherapy can sensitize iCBT, but its development was largely hindered by inefficient delivery and high requirements of storage. In this study, the vaccine loaded with immunostimulant was employed to improve iCBT-based adjuvant postsurgical therapy. A lyophilized, antigen E7 peptide and manganese ion (Mn²⁺) co-delivered tumor vaccine was developed based on lipid nanoparticles (EM@LNP). The vaccination efficacy was examined in both prophylactic and therapeutic schemes in murine subcutaneous models, the synergetic effect of vaccination combined with anti-PD-1 therapy was further investigated in post-operative tumor model. EM@LNP vaccination elicited effective CD8⁺T cell response through modulating tumor immunosuppressive microenvironment and conferring immune memory, demonstrating potent immunization in both preventive and therapeutic schemes. What's more, EM@LNP vaccination orchestrated with iCBT, efficiently repressing tumor recurrence. Further mechanism studies using inhibitor for cells invitro and the investigation using STING^-/- mice confirmed that the cGAS-STING signaling pathway activated by Mn²⁺ is indispensable for LNP vaccination and the coordination with iCBT-based adjuvant immunotherapy. In summary, this study shows a lyophilized LNP vaccine could significantly amplify iCBT efficiency, providing a translational strategy of adjuvant immunotherapy for treating postsurgical tumor recurrence.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"379"},"PeriodicalIF":10.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142764","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":"Oral administration of probiotic spores-based biohybrid system for efficient attenuation of Salmonella Typhimurium-induced colitis.","authors":"Mengya Niu, Luo Zhao, Shuang Gong, Xinxin Liu, Cuixia Zheng, Jiannan Jiao, Fangfang Wang, Lei Wang","doi":"10.1186/s12951-025-03468-x","DOIUrl":"10.1186/s12951-025-03468-x","url":null,"abstract":"<p><p>Salmonella Typhimurium (S. Tm), a Gram-negative pathogenic bacterium, is one of the most common causes of invasive bacterial diseases. Antibiotic therapy remains the principal therapeutic modality for treating S. Tm infection. However, due to the difficulty in precisely targeted pathogenic bacteria after oral administration, the therapeutic effect remains unsatisfactory. Here, we developed an oral probiotic spores-based biohybrid delivery system (BCs@PME-Au) to treat S. Tm-induced colitis. By employing a one-pot metal deposition method, Polymyxin E (PME) acted as a reducing agent to promote the Au³⁺ rapid nucleation and growth into PME-capped Au NPs (PME-Au NPs). By forming Au-S and Au-N bonds with the active sites (-SH, -NH₂) of Bacillus coagulans spores (BCs), PME-Au NPs were anchored onto the surface of BCs to construct the biohybrid system BCs@PME-Au. Following oral administration, BCs@PME-Au successfully passed through the gastric acid barrier. After absorbed water and nutrients, BCs germinated into Bacillus coagulans (BC) in the gut and PME-Au NPs were released. Based on the BC's targeting pathogen infection site and PME-Au NPs' targeting Gram-negative bacteria, the biohybrid system achieved significantly antibacterial effect of S. Tm. Mechanistically, by blocked the LPS-induced inflammatory pathway TLR4/MyD88/NF-κB, BCs@PME-Au exerted a powerful anti-inflammatory effect. With its robust antibacterial efficacy, targeted delivery, and excellent safety profile demonstrated both in vitro and in vivo, the biohybrid system BCs@PME-Au offers significant promise in treating bacterial colitis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"378"},"PeriodicalIF":10.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142767","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":"From bench to bedside: the research status and application opportunity of extracellular vesicles and their engineering strategies in the treatment of skin defects.","authors":"Longwei Cui, Yantao Song, Zhipeng Hou, Liqun Yang, Shu Guo, Chenchao Wang","doi":"10.1186/s12951-025-03461-4","DOIUrl":"10.1186/s12951-025-03461-4","url":null,"abstract":"<p><p>Engineered extracellular vesicles (EVs), which are EVs modified to enhance certain biological properties, offer a promising therapeutic strategy for the treatment of skin defects. Conventional nanomaterials often encounter clinical translation challenges due to potential toxicity and limited targeting. Engineered EVs, utilizing inherent biocompatibility and effective physiological barrier traversal, can ameliorate the limitations of conventional EV therapies to some extent, including detection, isolation, purification, and therapeutic validation. Recent advances in EV engineering, such as genetic modification of production cells to control cargo, surface engineering for targeted delivery, and pre-treatment of parental cells to optimize production and bioactivity, have improved therapeutic efficacy in laboratory studies through enhanced targeting, prolonged retention time, and increased yield. Many studies have suggested the potential ability of engineered EVs to treat a variety of skin defects, including diabetic wounds, burns, and hypertrophic scars, providing a promising avenue for their clinical translation in this area. This paper reviews the therapeutic potential of engineered EVs in skin regeneration, highlighting their role in promoting cell migration and angiogenesis, modulating inflammation and reducing scar formation during wound healing. In addition, given the investment in this rapidly evolving field and the growing clinical trial activity, this review also explores recent global advances and provides an outlook on future application opportunities for EVs in the treatment of skin defects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"375"},"PeriodicalIF":10.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142766","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":"An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism.","authors":"Chuan Yang, Langlang Xie, Zihan Deng, Hongbo Ai, Tingwen Xiang, Xiaojing Yan, Zhiguo Ling, Shiyu Xiao, Yong Tang, Gang Huang, Fei Luo, Yueqi Chen","doi":"10.1186/s12951-025-03450-7","DOIUrl":"10.1186/s12951-025-03450-7","url":null,"abstract":"<p><p>Dysbiosis of gut microbiota significantly exacerbates the progression of rheumatoid arthritis (RA). Targeting gut microbiota may present a promising therapeutic strategy for RA. Gold nanospheres (GNS), known for excellent biocompatibility, stability and minimal toxicity, have emerged as precise modulators of gut microbiota, reshaping intestinal environments to treat various inflammatory diseases. Our study found that oral administration of 60-nm GNS effectively ameliorated collagen-induced arthritis (CIA) in mice, with a marked reduction in disease severity and synovial inflammation. Specifically, GNS notably enriched the probiotic genus Ligilactobacillus while restoring intestinal barrier function by upregulating tight junction proteins Claudin-1 and ZO-1. Targeted metabolomics analysis revealed GNS substantially increased the production of indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in gut, which were shown to activate the aryl hydrocarbon receptor (AhR) pathway. Mechanistic studies demonstrated that the IPA/IAA mixture inhibited PTEN ubiquitination, stabilizing PTEN protein levels and suppressing NF-κB activation in synovial tissues. These changes correlated with reduced synovial hyperplasia and inflammatory infiltration. Our findings established GNS as an effective nanomodulator of the gut-joint axis, providing novel insights into microbiota-targeted therapies for RA and other inflammatory diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"376"},"PeriodicalIF":10.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142765","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":"Tumor microenvironment responsive Mn-based nanoplatform activate cGAS-STING pathway combined with metabolic interference for enhanced anti-tumor therapy.","authors":"E Wen, Yu Tian, Yu Chen, Zhigang Wang, Yi Feng, Zhen Liao","doi":"10.1186/s12951-025-03453-4","DOIUrl":"10.1186/s12951-025-03453-4","url":null,"abstract":"<p><p>Despite the encouraging developments in tumor immunotherapy, the complex tumor microenvironment (TME) and abnormal energy metabolism persist as key factors facilitating immune escape. Recent research has emphasized the significant potential of the Manganese ions (Mn²⁺) as a \"immune ion reactors\" have the potential to stimulate cGAS-STING signaling pathway in modulating tumor immunotherapy. However, their efficacy is limited by insufficient targeting and lack of tumor specificity. To address these challenges, we have developed a nano-drug named as LT@MnO@MON-HA (LMMH), which incorporates manganese oxide (MnO) nanoparticles as the core and organic mesoporous silica as the outer layer. The mitochondrial glycolysis inhibitor lonidamine (LT) is encapsulated within the mesopores of LMMH and subsequently coated with hyaluronic acid to achieve precise tumor-targeted drug delivery. After reaching the tumor site, LMMH can decompose in the reducing and acidic TME, releasing LT and Mn²⁺. Once internalized by cells, LT rapidly localizes to mitochondria via functional groups, disrupting mitochondrial metabolism and increasing intracellular reactive oxygen species levels. Mn²⁺ catalyze the conversion of hydrogen peroxide (H₂O₂) into more cytotoxic hydroxyl radicals (·OH), thereby enhancing chemodynamic therapy (CDT). The mesoporous silica shell of LMMH is capable of depleting glutathione in the TME, enhancing CDT. Moreover, LMMH functions as an agonist of the cGAS-STING pathway, stimulating cytokine release and activating effector T cells, which in turn triggering systemic immune responses against primary and metastatic cancers. Collectively, these finding highlights the dual mechanisms by which LMMH enhances combination immunotherapy by regulating the TME and tumor metabolism.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"377"},"PeriodicalIF":10.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142768","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}