{"title":"巨噬细胞和T细胞协同抗肿瘤的双重刺激反应纳米免疫调节剂","authors":"Junying Ding, Xueze Zhao, Saran Long, Wen Sun, Jianjun Du, Jiangli Fan, Xiaojun Peng","doi":"10.1021/acsnano.4c17285","DOIUrl":null,"url":null,"abstract":"Only a minority of patients benefit from current T-cell-focused adaptive immunotherapies, underscoring the need to engage innate immune cells, particularly macrophages, for multilayered tumor control. However, high-efficacy therapeutics capable of orchestrating multiple immune cells remain scarce. Herein, a dual stimuli-responsive nanoimmunomodulator (6EPP@si) that caters specifically to the tumor microenvironment (TME) is presented for the antitumor synergy of macrophages and T cells. Using the functional polymer-based carrier, we co-deliver the endoplasmic reticulum (ER)-localized photosensitizer 6E and small interfering RNA targeting CD47 (siCD47) into breast tumors. Within the acidic and high-glutathione TME, 6EPP@si undergoes self-lysosome escape and nanocleavage for precise, on-demand drug release. Consequently, siCD47 released into the cytoplasm enables potent CD47 silencing, while the ER-targeted photosensitizer 6E induces immunogenic cell death through reactive oxygen species-based ER stress, triggering the release of damage-associated molecular patterns, including calreticulin surface translocation. 6EPP@si enhances macrophage phagocytosis by modulating both antiphagocytic and prophagocytic signals and also promotes antigen presentation to activate T cells. In orthotopic breast tumor and spontaneous lung metastatic tumor models, this combined approach demonstrates robust antitumor effects and effective antimetastatic immunity, offering a meaningful strategy to simultaneously activate multiple immune cells for enhancing cancer immunotherapy.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"29 1","pages":""},"PeriodicalIF":16.0000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Dual Stimuli-Responsive Nanoimmunomodulator for Antitumor Synergy of Macrophages and T Cells\",\"authors\":\"Junying Ding, Xueze Zhao, Saran Long, Wen Sun, Jianjun Du, Jiangli Fan, Xiaojun Peng\",\"doi\":\"10.1021/acsnano.4c17285\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Only a minority of patients benefit from current T-cell-focused adaptive immunotherapies, underscoring the need to engage innate immune cells, particularly macrophages, for multilayered tumor control. However, high-efficacy therapeutics capable of orchestrating multiple immune cells remain scarce. Herein, a dual stimuli-responsive nanoimmunomodulator (6EPP@si) that caters specifically to the tumor microenvironment (TME) is presented for the antitumor synergy of macrophages and T cells. Using the functional polymer-based carrier, we co-deliver the endoplasmic reticulum (ER)-localized photosensitizer 6E and small interfering RNA targeting CD47 (siCD47) into breast tumors. Within the acidic and high-glutathione TME, 6EPP@si undergoes self-lysosome escape and nanocleavage for precise, on-demand drug release. Consequently, siCD47 released into the cytoplasm enables potent CD47 silencing, while the ER-targeted photosensitizer 6E induces immunogenic cell death through reactive oxygen species-based ER stress, triggering the release of damage-associated molecular patterns, including calreticulin surface translocation. 6EPP@si enhances macrophage phagocytosis by modulating both antiphagocytic and prophagocytic signals and also promotes antigen presentation to activate T cells. In orthotopic breast tumor and spontaneous lung metastatic tumor models, this combined approach demonstrates robust antitumor effects and effective antimetastatic immunity, offering a meaningful strategy to simultaneously activate multiple immune cells for enhancing cancer immunotherapy.\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"29 1\",\"pages\":\"\"},\"PeriodicalIF\":16.0000,\"publicationDate\":\"2025-02-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1021/acsnano.4c17285\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.4c17285","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
A Dual Stimuli-Responsive Nanoimmunomodulator for Antitumor Synergy of Macrophages and T Cells
Only a minority of patients benefit from current T-cell-focused adaptive immunotherapies, underscoring the need to engage innate immune cells, particularly macrophages, for multilayered tumor control. However, high-efficacy therapeutics capable of orchestrating multiple immune cells remain scarce. Herein, a dual stimuli-responsive nanoimmunomodulator (6EPP@si) that caters specifically to the tumor microenvironment (TME) is presented for the antitumor synergy of macrophages and T cells. Using the functional polymer-based carrier, we co-deliver the endoplasmic reticulum (ER)-localized photosensitizer 6E and small interfering RNA targeting CD47 (siCD47) into breast tumors. Within the acidic and high-glutathione TME, 6EPP@si undergoes self-lysosome escape and nanocleavage for precise, on-demand drug release. Consequently, siCD47 released into the cytoplasm enables potent CD47 silencing, while the ER-targeted photosensitizer 6E induces immunogenic cell death through reactive oxygen species-based ER stress, triggering the release of damage-associated molecular patterns, including calreticulin surface translocation. 6EPP@si enhances macrophage phagocytosis by modulating both antiphagocytic and prophagocytic signals and also promotes antigen presentation to activate T cells. In orthotopic breast tumor and spontaneous lung metastatic tumor models, this combined approach demonstrates robust antitumor effects and effective antimetastatic immunity, offering a meaningful strategy to simultaneously activate multiple immune cells for enhancing cancer immunotherapy.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.