{"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}
Hui Liu, Haoyu Wan, Anbiao Zhang, Yi Ouyang, Xinya Lu, Mengyuan Wu, Ning Hu, Jianying Pan, Dong Guo, Zhong Alan Li, Denghui Xie
{"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, Fe<sup>3+</sup> reacts with intracellular over-expressed glutathione to form Fe<sup>2+</sup>, 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, PO<sub>4</sub><sup>3-</sup> 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}
{"title":"Zinc-doped curcumin carbon dots promote infected wound healing with photodynamic via the VEGF signaling pathway.","authors":"Yifan Zhao, Jia Liu, Lingxiang Sun, Haiyan Liu, Xi Chen, Xuedong Deng, Yilin Ping, Wenze Han, Jing Wang, Feng Tian, Jingyu Yan, Xiuping Wu, Bing Li","doi":"10.1186/s12951-025-03509-5","DOIUrl":"10.1186/s12951-025-03509-5","url":null,"abstract":"<p><p>Management of bacterial infected wounds remains challenging due to the open, susceptibility to infection and delayed healing characteristics of damaged wounds, and there is an urgent need for non-antibiotic-based wound healing strategies. Here, we describe zinc-doped curcumin carbon dots (CCDs) as a novel nanoscale photosensitizer, which was applied in photodynamic therapy (PDT) to promote infected wound healing by modulating various cellular functions. The PDT generation of reactive oxygen species (ROS) effectively inactivates the source of infection without drug resistance, effectively inhibiting the propagation of bacteria and the spread of inflammation in the wound. In addition, CCDs have the ability to promote cell proliferation and extension, accelerate blood vessel formation and collagen deposition, and significantly improve wound healing efficiency by modulating the VEGF signaling pathway. These features create a favorable environment for skin regeneration and synergistically accelerate infected wound healing. We believe it has great potential to address antibiotic misuse and effectively manage infected wounds.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"424"},"PeriodicalIF":10.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248311","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":"The effects of Klotho delivering mesenchymal stem cell-derived small extracellular vesicles on acute kidney injury.","authors":"Xiao-Hui Deng, Zi-Cong Wu, Qi Sun, Long-Xin Huang, Ying-Chun Xie, Dong-Xiao Lou, Chan-Gu Li, Xiao-Qing Liu, Zhi-Rou Zhou, Tian Tian, Chang-Lin Lian, Qing-Ling Fu","doi":"10.1186/s12951-025-03499-4","DOIUrl":"10.1186/s12951-025-03499-4","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a life-threating syndrome characterized by sudden loss of kidney function, and its management is challenging and often suboptimal. Mesenchymal stem cells (MSCs) have shown promise in AKI therapy in pre-clinical and clinical trials; however, their clinical application still faces many challenges. MSC-derived small extracellular vesicles (sEV) may help overcome these challenges. In the current study, we overexpressed Klotho in MSCs and then isolated Klotho-loaded sEV (Klotho-sEV) using anion-exchange chromatography. Klotho-sEV displayed characteristics comparable to those of sEV in terms of size, morphology, conventional markers, and biosafety, as well as a higher abundance of Klotho protein. In rhabdomyolysis-induced AKI, sEV showed preferential tropism in injured kidneys. We found significantly and stably accelerated renal recovery, mitigated functional and histological abnormalities, stimulated tubular cell proliferation, reduced injury and inflammatory marker expression, and restored endogenous Klotho loss in mice after the administration of Klotho-sEV. In addition, Klotho-sEV treatment activated the mTOR and MEK1/2 signaling pathways. Proteomics and small RNA sequencing analyses of sEV and Klotho-sEV revealed abundant proteins and miRNAs involved in anti-inflammation and reno-protection, and Klotho-sEV showed characteristics that were different from those of sEV. In conclusion, Klotho-sEV may be a promising cell-free strategy for the treatment of AKI.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"427"},"PeriodicalIF":10.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248309","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}
Michalina Miszczak, Kabiruddin Khan, Pernille Høgh Danielsen, Keld Alstrup Jensen, Ulla Vogel, Roland Grafström, Agnieszka Gajewicz-Skretna
{"title":"Dynamic QSAR modeling for predicting in vivo genotoxicity and inflammation induced by nanoparticles and advanced materials: a time-dose-property/response approach.","authors":"Michalina Miszczak, Kabiruddin Khan, Pernille Høgh Danielsen, Keld Alstrup Jensen, Ulla Vogel, Roland Grafström, Agnieszka Gajewicz-Skretna","doi":"10.1186/s12951-025-03510-y","DOIUrl":"10.1186/s12951-025-03510-y","url":null,"abstract":"<p><p>Predicting the health risks of nanoparticles (NPs) and advanced materials (AdMa) is a critical challenge. Due to the complexity and time-consuming nature of experimental testing, there is a reliance on in silico methods such as quantitative structure-activity relationship (QSAR), which, while effective, often fail to capture the dynamic nature of material activity over time-essential for reliable risk assessment. This study develops dynamic QSAR models using machine learning to predict toxicological responses, such as inflammation and genotoxicity, following pulmonary exposure to 39 AdMa across various post-exposure time points and dose levels. By incorporating exposure time, administered dose, and material properties as independent variables, we successfully developed time-dose-property/response models capable of predicting AdMa-induced in vivo genotoxicity in bronchoalveolar lavage fluid cells, lung and liver tissue, and inflammation in terms of neutrophil influx into the lungs of mice. Key factors driving AdMa-induced toxicity were identified, including exposure dose, post-exposure duration time, aspect ratio, surface area, reactive oxygen species generation, and metal ion release. The time-dose-property/response modeling paradigm presented here provides a practical and robust approach for predicting in vivo genotoxicity and inflammation and supports the comprehensive risk assessment of morphologically diverse AdMa.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"420"},"PeriodicalIF":10.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248281","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":"Targeting Dicer reprograms tumor-associated macrophages to promote anti-tumoral immunity in colorectal cancer liver metastasis.","authors":"Shenglong Xia, Wenwen Chen, Zhengyang Xu, Yuzhen Gao, Jingyu Chen, Ning Ding, Ying Zhang, Tianhua Zhou, Xuefei Zhou, Xiangrui Liu, Meng Xue","doi":"10.1186/s12951-025-03518-4","DOIUrl":"10.1186/s12951-025-03518-4","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages (TAMs) contribute significantly to immunosuppression in colorectal cancer liver metastasis (CRLM), leading to high aggressiveness and poor prognosis. However, the key molecules involved in shaping TAMs toward the pro-tumoral phenotype in CRLM remain unclear, limiting the development of macrophage-mediated immunotherapies for CRLM.</p><p><strong>Results: </strong>In this study, we showed that DICER1 was highly expressed in TAMs and closely associated with M2 polarization in CRLM. Knockdown of Dicer, encoded by DICER1 in humans (or Dicer1 in mice), skewed macrophages toward an anti-tumoral M1 phenotype, with increased expression of pro-inflammatory cytokines and tumor cell phagocytosis, thereby suppressing tumor growth in mice. An M2 macrophage-targeting nanosystem was developed to deliver Dicer1 siRNA for selectively downregulating Dicer expression in M2 macrophages. In situ manipulation of TAMs with the nanoparticle exerted a significant anti-tumor effect with an improved immune microenvironment in a CRLM mouse model. Macrophage depletion experiments further suggested that this effect was largely dependent on the presence of TAMs. Mechanistically, Dicer inhibition reprogrammed M2-like macrophages through downregulation of miR-148a-3p and miR-1981-5p.</p><p><strong>Conclusion: </strong>Our study uncovered the central role of Dicer in the M2 polarization of TAMs, in turn suggesting a promising therapeutic strategy for CRLM.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"421"},"PeriodicalIF":10.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248308","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}
Shaobo Bai, Yang Sun, Miao Liu, Ying Cheng, Qifeng Ji, Bangle Zhang, Zhifu Yang, Siyuan Zhou, Daozhou Liu
{"title":"Automatic target-seeking nanoparticle inhibiting orthotopic drug-resistant colon cancer and liver metastases via regulating cancer cell adhesion and proliferation.","authors":"Shaobo Bai, Yang Sun, Miao Liu, Ying Cheng, Qifeng Ji, Bangle Zhang, Zhifu Yang, Siyuan Zhou, Daozhou Liu","doi":"10.1186/s12951-025-03422-x","DOIUrl":"10.1186/s12951-025-03422-x","url":null,"abstract":"<p><p>Galectin-3 (Gal-3) plays an important role in adhesion and proliferation of cancer cells. The level of Gal-3 in blood and the expression of Gal-3 in colon cancer tissue are significantly increased in patient with colon cancer. The elevated Gal-3 promotes the migration and drug resistance of colon cancer. Therefore, Gal-3 is a promising target to inhibit the growth and metastases of cancer cells. Besides, integrin αvβ3, a receptor of Gal-3, is highly expressed in colon cancer cell and blood vessel in colon cancer tissue. In this paper, an automatic target-seeking nanoparticle (SP@MCaP) contained siGal-3 and paris saponin VII (PSVII) was prepared. In vivo, by automatically capturing Gal-3 in the blood circulation, SP@MCaP actively recognized cancer tissue vessel and drug-resistant colon cancer cells with elevated integrin αvβ3 expression, resulting in specifical accumulation in orthotopic drug-resistant colon cancer tissue. SP@MCaP diminished Gal-3 level in serum and orthotopic drug-resistant colon cancer tissue, and then suppressed the proliferation of drug-resistant colon cancer cells. Importantly, SP@MCaP reconstructed the adhesion of drug-resistant colon cancer cells and reversed the immunosuppressive microenvironment in orthotopic drug-resistant colon cancer tissue and liver tissue. Finally, under the synergistic effect of siGal-3 and PSVII, SP@MCaP successfully inhibited the growth of orthotopic drug-resistant colon cancer and its liver metastases. In a word, this paper explored a novel concept of the active co-delivery of siGal-3 and PSVII by modification of nanoparticle, which holds promise for targeted therapy in orthotopic drug-resistant colon cancer and its liver metastases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"423"},"PeriodicalIF":10.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248280","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 nanomodulator for near infrared photothermal immunotherapy of hepatocellular carcinoma.","authors":"Fei Kong, Tian Xia, Xiaorong Zhu, Xueping Zeng, Fengyu Wang, Jianxin Lyu, Lisen Lu, Zhen Wang","doi":"10.1186/s12951-025-03440-9","DOIUrl":"10.1186/s12951-025-03440-9","url":null,"abstract":"<p><p>Recurrence and metastasis remain significant challenges in the clinical treatment of hepatocellular carcinoma (HCC). The integration of photodynamic therapy and immunotherapy has emerged as a promising strategy for treating cancer in terms of safety and efficacy. However, conventional photodynamic therapy and anti-tumor immunotherapy face several limitations, including inadequate light source penetration, poor targeting precision, low response rates, and immune-related adverse effects. To address these issues, we developed a tumor microenvironment responsive polymer nano-immunomodulator for precise photodynamic immunotherapy of HCC. The nano-immunomodulator is self-assembled from glutathione responsive amphiphilic polymers (TPS) and pH-activatable photosensitizers (LET-Br), and is further loaded with the anticancer drug docetaxel. Additionally, it is conjugated with small-molecule agonists of Toll-like receptor 7/8 (TLR 7/8) and cyclic RGD (cRGD) targeting peptides. Upon reaching the tumor site, the PNI undergoes hydrolysis, enabling the efficient release of anticancer drugs in response to the tumor microenvironment. Furthermore, under near-infrared (NIR) photoirradiation, the PNI exerts potent photodynamic effects to directly eliminate tumors. Remarkably, the PNI also functions as an in situ light-activated cancer vaccine, capable of inducing systemic antitumor immune responses and remodeling the immunosuppressive tumor microenvironment to establish long-lasting immune memory. This synergistic combination of photodynamic therapy and targeted antitumor immune responses effectively inhibits tumor growth. Thus, this study not only presents a novel strategy for designing vaccine-like prodrugs to precisely modulate cancer immunotherapy, but also opens new avenues for the development of advanced therapies for HCC.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"417"},"PeriodicalIF":10.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234380","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}