Journal of Nanobiotechnology最新文献

{"title":"Gambogic acid-iron nanozymes as effective carriers for enhanced chemotherapy by inducing excessive autophagy and oxidative stress.","authors":"Yang Qiao, Menghui Liu, Yiqun Zhang, Fan Ni, Liangchen Yu, Zhao Chen, Xingliang Dai, Xianwen Wang","doi":"10.1186/s12951-025-03519-3","DOIUrl":"https://doi.org/10.1186/s12951-025-03519-3","url":null,"abstract":"<p><p>The complex dual role of autophagy provides new insights for enhancing tumor treatment efficacy. However, effectively regulating this process is key to enhancing therapeutic efficacy. To address this challenge, this study designed a gambogic acid-iron nanozyme (GAFe) as a novel carrier to enhance the effectiveness of chemotherapy drugs such as doxorubicin (DOX) by inducing excessive autophagy and oxidative stress. The synthesized nanoparticle (GAFe@DOX) is capable of slowly releasing its active components over a prolonged period within tumor tissues. Gambogic acid can induce excessive autophagy, while the multi-enzyme activity of GAFe and the activation of ferroptosis amplify and sustain excessive autophagy, thereby enhancing the chemotherapy effect of DOX. Meanwhile, ferroptosis activated via the GPX4 pathway by GAFe can synergize with excessive autophagy, amplifying oxidative stress and consequently enhancing the overall therapeutic efficacy. Characterization experiments confirmed the successful synthesis of GAFe@DOX and probe assays demonstrated its superior multi-enzyme activity. In vitro cell studies showed that GAFe@DOX effectively kills tumor cells, while in vivo animal experiments revealed its excellent biocompatibility and significant tumor growth inhibition. This study demonstrates a promising strategy to improve tumor therapeutic efficacy by modulating excessive autophagy and oxidative stress. This provides a novel and effective approach to improve the treatment of refractory tumors such as glioblastoma.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"435"},"PeriodicalIF":10.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atractylodes macrocephala-derived extracellular vesicles-like particles enhance the recovery of ulcerative colitis by remodeling intestinal microecological balance.","authors":"Xuejun Tan, Bowen Gao, Yukun Xu, Qing Zhao, Jiazan Jiang, Dexuan Sun, Yirong Zhang, Sirui Zhou, Jun-Bing Fan, Mingzhen Zhang, Kewei Zhao","doi":"10.1186/s12951-025-03506-8","DOIUrl":"https://doi.org/10.1186/s12951-025-03506-8","url":null,"abstract":"<p><p>Current treatment of ulcerative colitis (UC) remains challenging, with the mainstay of therapy being 5-aminosalicylic acid-based drugs, which have limited and inconsistent results. Atractylodes macrocephala (AM) is a traditional Chinese medicine commonly used in the clinical treatment of various inflammatory diseases. Herein, we demonstrate that AM-derived extracellular vesicle-like particles (AMEVLP) can effectively modulate the gut microbiota, thereby significantly improving the treatment efficiency of UC. This is achieved by enhancing the alpha diversity of the gut microbiota and re-establishing beneficial types, which in turn alter tryptophan metabolism, leading to an increase in indole derivatives within the gut. This process also protects the gut barrier and exerts anti-inflammatory effects. The mechanism behind these anti-inflammatory effects is closely associated with the Th17 cell differentiation signaling pathway. It is believed that the AMEVLP enable them to efficiently remodel gut microbiota, providing an avenue for the treatment of various inflammatory diseases. Significantly, preliminary clinical trials have shown that AMEVLP can substantially slow the progression of the disease in UC patients.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"433"},"PeriodicalIF":10.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretome enriched with small extracellular vesicles derived from human gingiva-derived mesenchymal stem cells enhances rat tongue muscle regeneration.","authors":"Qunzhou Zhang, Puhan He, Shihong Shi, Qilin Xu, Eric J Granquist, Beth A Winkelstein, Rabie M Shanti, Anh D Le","doi":"10.1186/s12951-025-03515-7","DOIUrl":"https://doi.org/10.1186/s12951-025-03515-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Accumulating evidence demonstrates that the therapeutic effects of stem cells are most likely attributed to their secretome, composed of a myriad of bioactive factors, including small extracellular vesicles (EVs). Due to the potential benefits over cells in term of handling, preservation, stability, and safety, MSC-derived secretome is emerging as a novel cell-free therapeutic for regenerative therapy of various diseases. The purpose of this study is to optimize the xeno-free culture conditions to improve the secretome production by human gingiva-derived mesenchymal stem cells (GMSCs) and test their regenerative potential using an experimental rat model of tongue muscle defect.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Next-generation mRNA sequencing was performed to compare the gene expression profiles between GMSCs cultured under the defined xeno-free induction culture conditions (iGMSCs) and their 2D-cultured counterparts under regular serum-free conditions. The conditioned media (CM) from iGMSCs and 2D-GMSCs were harvested and concentrated through ultrafiltration to obtain secretomes. The EVs and soluble protein/peptide factor fractions (SPs) from the concentrated CM/secretome were separated using the 35 nm qEVoriginal size exclusion columns. The EVs were confirmed by Nanoparticle Tracking Analysis (NTA), Western blot, and transmission electron microscopy (TEM). The functional effects of secretomes derived from iGMSCs and 2D-GMSCs on macrophage polarization and skeletal muscle progenitor cells were compared both in vitro and in vivo using a rat tongue defect model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Next-generation mRNA sequencing showed profound transcriptomic changes in iGMSCs compared to their 2D counterparts. Further Gene Ontology (GO)-term annotation and Gene Set Enrichment Analysis (GSEA) revealed significant upregulation of a panel of differentially expressed genes (DEGs) related to EVs and secreted cellular components (GO_CCs) and enriched pathways in oxidative phosphorylation, Wnt/β-catenin signaling, Notch signaling, and inflammatory responses in iGMSCs compared to 2D-GMSCs. iGMSC-derived CM/secretome showed a significant enrichment of both EVs and SPs compared to that derived from 2D-GMSCs, as confirmed by Nanoparticle Tracking Analysis (NTA), Western blot, and transmission electron microscopy (TEM). In vitro functional assays revealed a markedly enhanced secretion of IL-10, whilst suppressed LPS-stimulated secretion of TNF-α in macrophages treated with iGMSC-derived CM/secretome in comparison with that from 2D-GMSCs. In addition, iGMSC-derived CM/secretome potently induced the expression of myogenic transcriptional factors in both murine myoblasts and human skeletal muscle progenitors in comparison with 2D-GMSC-derived CM/secretome. Notably, in vivo studies using a rat tongue wound defect model, iGMSC-derived CM/secretome applied topically at the excised wound bed promoted rapid tissue repair/regeneration withou","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"434"},"PeriodicalIF":10.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor/anti-inflammatory effects/tissue healing as an all-in-one therapeutic strategy for nasopharyngeal carcinoma.","authors":"Fan Ni, Hanxin Lv, Liting Lin, Yiqun Zhang, Yang Qiao, Xiaopei Zhang, Zengyang Li, Xianwen Wang, Xingliang Dai, Jun Dong","doi":"10.1186/s12951-025-03520-w","DOIUrl":"https://doi.org/10.1186/s12951-025-03520-w","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is one of the most prevalent cancers in the head and neck region. The development of innovative therapies that are effective at eliminating tumors while minimizing damage to surrounding normal tissues due to postoperative complications is crucial. To solve this problem, a gelatin-sodium alginate (Gel-SA) hydrogel containing bismuth selenide nanosheets (Bi₂Se₃ NSs) has been developed, which introduces a \"switch\" of near-infrared (NIR) light for photodynamic therapy (PDT) and photothermal therapy (PTT) to significantly increase the level of oxidative stress while inducing ferroptosis and apoptosis to synergistically treat tumors. Once the treatment of the tumor has been completed, NSs remove a large number of free radicals left by NIR irradiation because of their excellent anti-inflammatory performance and combine with the rich nutrients in Gel-SA to protect and repair the tissues around the tumor. Combining Bi₂Se₃ NSs and Gel-SA is an effective solution for treating NPC, as it ablates tumors while protecting surrounding tissues.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"431"},"PeriodicalIF":10.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sonodynamic therapy-boosted biomimetic nanoplatform targets ferroptosis and CD47 as vulnerabilities for cancer immunotherapy.","authors":"Haiqin Liao, Mingyu Chen, Zhipeng Liao, Yi Luo, Sijie Chen, Wanlin Tan, Long Wang, Chengcheng Niu","doi":"10.1186/s12951-025-03485-w","DOIUrl":"https://doi.org/10.1186/s12951-025-03485-w","url":null,"abstract":"<p><p>The efficacy of cancer immunotherapy is frequently hindered by the immunosuppressive \"cold\" tumor microenvironment. Inducing immunogenic cell death (ICD) may address this limitation. Ferroptosis, a form of ICD characterized by iron-dependent lipid peroxidation, has gained attention as a therapeutic target due to its inherent or therapy-induced susceptibility in refractory cancers and resistant tumor microenvironments. CD47, overexpressed on tumor cell membranes, enables immune evasion by suppressing macrophage-mediated surveillance, positioning it as a promising immune checkpoint target for macrophage-driven immunotherapy. Combining ferroptosis induction with CD47 blockade represents a strategic approach to enhance therapeutic outcomes. In this study, we developed a biomimetic nanoplatform-IR780/MnO₂@PLGA@cell membrane-PEP20 nanoparticles-featuring a shell derived from 4T1 cell membranes conjugated with the CD47-inhibitory peptide PEP20. This design enables tumor-targeted delivery while enhancing macrophage phagocytosis of tumor cells. The MnO₂ core depletes intra-tumoral glutathione, downregulating glutathione peroxidase 4 and accumulating lipid peroxides to trigger ferroptosis. Concurrently, the ultrasound-responsive agent IR780 generates singlet oxygen under ultrasound irradiation, amplifying ferroptosis via oxidative stress. The resultant reactive oxygen species drive M2-to-M1 macrophage repolarization. Ferroptosis-mediated ICD further stimulates dendritic cell antigen presentation, activates cytotoxic T-cell immunity, and establishes durable immune memory. By exploiting tumor defense mechanisms as therapeutic vulnerabilities, this nanoplatform offers an innovative strategy for refractory cancer treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"432"},"PeriodicalIF":10.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Size-tuned PEGylated NIR-II fluorescent probes for high-contrast plant imaging and TMV detection.","authors":"Fang Zhao, Yu-Ling Xu, Meng-Jiao Lu, Le Tu, Chong-Lu Li, You Dou, Jun Li, Xiang-Yang Li, Yao Sun","doi":"10.1186/s12951-025-03452-5","DOIUrl":"10.1186/s12951-025-03452-5","url":null,"abstract":"<p><p>The widespread applications of fluorescence imaging in plant science still suffer from challenges including strong auto-fluorescence (chlorophyll) and tissue light scattering, resulting in low signal-to-background ratio (SBR) for in vivo bioimaging. Moreover, the relationship between the transport efficacy of fluorescence probes in plants and their sizes has been rarely investigated. To address these bottlenecks, we developed an ingenious PEG-engineering strategy on the second near-infrared (NIR-II) donor-acceptor-donor (D-A-D) emissive dye (CCNU1020) to adjust the self-assembly nanosizes of NIR-II fluorescence probes, resulting in three variants: SYH1 (170 nm), SYH2 (80 nm), and SYH3 (60 nm). As the polyethylene glycol (PEG) chain length increased, the probes' nanosize decreased from 170 to 60 nm. Among them, SYH3 exhibited the fastest entry velocity into Epipremnum Aureum leaf and spread over the leaf veins evenly than the other two probes, of which SYH1 even could hardly entry into the leaf. Meanwhile, SYH3 demonstrated high-contrast imaging of leaf vein with an exceptional signal to background ratio (SBR, ~ 18.6) superior to that of classical NIR-I indocyanine green (ICG) (~ 3.0) and SYH2. This promising imaging ability of leaf veins achieved by size optimization laid the foundation for the early diagnosis of viral infections. In vivo experiments further confirmed that SYH3 effectively accumulated and monitored in the lesion of Tobacco mosaic virus (TMV)-infected Arabidopsis thaliana, which matched well with the green fluorescent protein (GFP)-labeled results. This work represents a significant step forward in plant bioimaging in the cutting-edge NIR-II region.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"430"},"PeriodicalIF":10.6,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248286","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 remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine.","authors":"Jing Bai, Mengzhen Wang, Yiming Luo, Biao Duan, Ying Yang, Yuting Fu, Shuqin Li, Zhongqian Yang, Peng Zheng, Tong Yu, Xin Yin, Hongmei Bai, Qiong Long, Yanbing Ma","doi":"10.1186/s12951-025-03471-2","DOIUrl":"10.1186/s12951-025-03471-2","url":null,"abstract":"<p><p>The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (ICD) in multiple mouse tumor cell lines. In this study, we further explored the potential impact of THIO on remodeling the tumor microenvironment, regulating anti-tumor immune responses, and its possible synergistic effects with other therapeutic methods, such as tumor vaccines. Our results showed that THIO could also induce ICD in various human tumor cell lines. The induction of ICD in tumor cells promoted the migration and maturation of antigen-presenting cells. Administration of THIO significantly inhibited the growth of established CT26 and TC-1 tumors in mice. Meanwhile, it enhanced the anti-tumor CTL response and reduced the levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) in both the spleen and tumor tissues. Additionally, THIO had a direct inhibitory effect on the proliferation and differentiation of MDSCs. Moreover, when combined with bacterial biomimetic vesicles or a nanovaccine, such as THIO with BBV or different Q11-tumor antigen peptide nanofibers, it exhibited enhanced anti-tumor effects and immune responses compared to monotherapy in either \"immune hot\" TC-1 tumors or \"immune cold\" B16-F10 tumors. In summary, THIO has the ability to remodel the tumor microenvironment, exert a specific killing effect on tumor cells, and effectively cooperate with tumor vaccines. This broadens the anti-tumor mechanisms of THIO and provides a promising strategy for improving anti-tumor immunotherapies.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"429"},"PeriodicalIF":10.6,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248310","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 plantarum-derived extracellular vesicles from dietary barley leaf supplementation attenuate Citrobacter rodentium infection and intestinal inflammation.","authors":"Yu Feng, Qian Zhao, Yifan Zhao, Chen Ma, Meiling Tian, Xiaosong Hu, Fang Chen, Daotong Li","doi":"10.1186/s12951-025-03504-w","DOIUrl":"10.1186/s12951-025-03504-w","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory disorder characterized by disturbed interactions between gut microbiota and host immune response. Barley leaf (BL) is a traditional Chinese herb recorded to have health-promoting effects. However, little is known about the beneficial role of BL against enteric infection-induced intestinal inflammation. Here, we uncover that BL protects against Citrobacter rodentium (C. rodentium)-induced infectious colitis by improving host-microbiota interactions.</p><p><strong>Methods: </strong>C3H/HeN mice were fed a diet with/without BL and infected with C. rodentium. Transcriptome sequencing, anti-CD4 antibody treatment, and flow cytometry were conducted to investigate the mechanisms of T cell immune modulation. The intervention involved administering anti-CD4 antibody at 500 µg each time for three times before and during C. rodentium infection. Analysis of gut microbiota composition was performed by 16S rRNA gene sequencing on fecal samples. Fecal microbiota transplantation was conducted by administering microbiota from donor group to recipient group via oral gavage to investigate the role of intestinal microbiota in immune modulation.</p><p><strong>Results: </strong>BL ameliorated the severity of C. rodentium-induced colitis, and this effect was linked to improved gut homeostasis and enhanced mucosal barrier function. BL enriched the pathways of T helper 1 (Th1)/Th2 and Th17 cell differentiation in the colon, suggesting the involvement of CD4⁺ T cells. Consistent with this, anti-CD4 antibody treatment abrogated the effect of BL and flow cytometry analysis revealed that BL mitigated C. rodentium-induced pro-inflammatory Th1 immune response. Moreover, the protective effect of BL was associated with alleviation of gut microbiota dysbiosis and increased abundance of Lactobacillus. Our in vivo studies further revealed that live Lactobacillus plantarum (L. plantarum) administration attenuated the pathogenic effects induced by C. rodentium infection, whereas heat-inactivated L. plantarum did not show the same results. Mechanistically, BL supplementation enriched L. plantarum, which subsequently released nanosized extracellular vesicles (EVs) that serve as a key mediator in alleviating C. rodentium-associated pathology and Th1 cell dysregulation.</p><p><strong>Conclusions: </strong>Our work thus provides evidence for utilizing BL and L. plantarum-derived EVs to manage enteric infection-associated IBD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"426"},"PeriodicalIF":10.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248283","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":"Genetically engineered T cell membrane-camouflaged nanoparticles triggered cuproptosis for synergistic bladder cancer photothermal-immunotherapy.","authors":"Wen Deng, Yuan Chen, Yongke Bai, Haojie Shang, Jian Wu, Zichen Zhong, Xiaozhuo Ba, Yonghua Tong, Yu He, Kehua Jiang, Kun Tang","doi":"10.1186/s12951-025-03511-x","DOIUrl":"10.1186/s12951-025-03511-x","url":null,"abstract":"<p><p>Immunotherapy has become a promising and transformative approach for treating advanced or treatment-resistant bladder cancer (BCa). However, its efficacy remains limited due to the immunosuppressive tumor microenvironment (TME) and insufficient immune cell infiltration. Photothermal therapy (PTT), which could cause immunogenic cell death (ICD) in tumor tissue, has been explored as a synergistic approach for bladder cancer immunotherapy. Yet, thermal resistance in cancer cells often undermines the effectiveness of PTT. To address these challenges, we proposed a novel strategy that combines PTT with cuproptosis, a recently identified form of ICD, by engineering Tim-3-overexpressing T cell membrane-coated nanoparticles (Tim3@PHSM@IC) to enhance BCa immunotherapy. The overexpression of Tim-3 on the T cell membrane enabled precise targeting of tumor cells and competitively inhibited the Tim-3 receptor on T cells through recognition of Galectin-9. In vitro, Tim3@PHSM@IC nanoparticles effectively induced photothermal cytotoxicity and robust cuproptosis. In vivo, these nanoparticles significantly inhibited tumor growth in multiple BCa mouse models. Flow cytometry (FCM) and RNA sequencing (RNA-seq) analyses revealed that Tim3@PHSM@IC nanoparticles reprogrammed the TME by activating immune-related genes and enhancing ICD This study highlights the potential of Tim3@PHSM@IC nanoparticles in overcoming the immunosuppressive TME and improving the efficacy of BCa immunotherapy by integrating PTT and cuproptosis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"425"},"PeriodicalIF":10.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248282","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":"Polypyrrole-ferric phosphate-methotrexate nanoparticles enhance apoptosis/ferroptosis of M1 macrophages via autophagy blockage for rheumatoid arthritis treatment.","authors":"Hui Liu, Haoyu Wan, Anbiao Zhang, Yi Ouyang, Xinya Lu, Mengyuan Wu, Ning Hu, Jianying Pan, Dong Guo, Zhong Alan Li, Denghui Xie","doi":"10.1186/s12951-025-03501-z","DOIUrl":"10.1186/s12951-025-03501-z","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an inflammatory disease that progresses from synovial inflammation to cartilage and bone destruction. Eliminating pro-inflammatory M1 macrophages is a promising strategy for RA treatment, but is impeded by cytoprotective autophagy. Herein, we report an effective autophagy blockage-promoted apoptosis/ferroptosis strategy using multifunctional ferric phosphate-decorated, methotrexate-loaded polypyrrole nanoparticles (PPy-FePi-MTX NPs) to achieve enhanced RA treatment effects. When injected into the knee joints of a collagen-induced DBA/1J mouse model of RA, the payloads on PPy NPs are released under the stimulation of an inflammatory microenvironment. The released MTX can directly induce M1 macrophage apoptosis. Upon near-infrared laser irradiation, the photothermal effect of PPy NPs further promotes cellular apoptosis. In addition, Fe³⁺ reacts with intracellular over-expressed glutathione to form Fe²⁺, which can convert hydrogen peroxide into toxic hydroxyl radicals. This redox process could deplete glutathione, inactivate glutathione peroxidase 4, and cause lipid peroxidation accumulation, resulting in ferroptosis of inflammatory M1 macrophages. Furthermore, PO₄^3- disrupts the normal function of lysosomes by pH disturbance, disabling the cytoprotective autophagy of M1 macrophages for enhanced anti-RA effects. This work develops multifunctional PPy NPs for RA treatment through effective elimination of pro-inflammatory M1 macrophage.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"428"},"PeriodicalIF":10.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248284","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}