{"title":"用于体内靶向mRNA递送的质量比控制器官选择性磷脂酰聚合物载体。","authors":"Hanqin Zhao,Yuxi Gao,Yibo Qi,An Ziyue,Minhui Li,Jie Chen,Sheng Ma,Wantong Song,Xuesi Chen","doi":"10.1021/acsnano.5c12386","DOIUrl":null,"url":null,"abstract":"Organ-selective mRNA transfection enables precise regulation of gene expression in specific tissues and represents a pivotal strategy for advancing mRNA therapeutics toward multiorgan and multi-indication applications. However, prevailing delivery systems rely on tissue-specific ligands or polyplex chemical modifications, limiting the modularity, scalability, and clinical translatability of delivery systems. Herein, we report a mass-ratio-controlled organ-selective (MACO) mRNA delivery platform based on phosphatidyl polyethylenimine derivatives (PEI-PPs). Impressively, the MACO platform enables precise and reversible switching of mRNA transfection among the spleen (94%), liver (78%), and lung (95%) by simply adjusting the mass ratio of PEI-PP to mRNA, without requiring additional targeting ligands, charge modifiers, or chemical modifications. Mechanistic investigations revealed that varying mass ratios generate polyplexes with distinct surface charge and pKa profiles, which in turn adsorb plasma protein coronas forming specific \"protein fingerprints\" that mediate organ-selective capability. The MACO mechanism represents the demonstration of organ-selective mRNA delivery governed solely by formulation parameters rather than polyplex structural alterations, providing a universal strategy to finely tune the mRNA multiorgan target.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"33 1","pages":""},"PeriodicalIF":16.0000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mass-Ratio-Controlled Organ-Selective Phosphatidyl Polymer Carrier for In Vivo Targeted mRNA Delivery.\",\"authors\":\"Hanqin Zhao,Yuxi Gao,Yibo Qi,An Ziyue,Minhui Li,Jie Chen,Sheng Ma,Wantong Song,Xuesi Chen\",\"doi\":\"10.1021/acsnano.5c12386\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Organ-selective mRNA transfection enables precise regulation of gene expression in specific tissues and represents a pivotal strategy for advancing mRNA therapeutics toward multiorgan and multi-indication applications. However, prevailing delivery systems rely on tissue-specific ligands or polyplex chemical modifications, limiting the modularity, scalability, and clinical translatability of delivery systems. Herein, we report a mass-ratio-controlled organ-selective (MACO) mRNA delivery platform based on phosphatidyl polyethylenimine derivatives (PEI-PPs). Impressively, the MACO platform enables precise and reversible switching of mRNA transfection among the spleen (94%), liver (78%), and lung (95%) by simply adjusting the mass ratio of PEI-PP to mRNA, without requiring additional targeting ligands, charge modifiers, or chemical modifications. Mechanistic investigations revealed that varying mass ratios generate polyplexes with distinct surface charge and pKa profiles, which in turn adsorb plasma protein coronas forming specific \\\"protein fingerprints\\\" that mediate organ-selective capability. The MACO mechanism represents the demonstration of organ-selective mRNA delivery governed solely by formulation parameters rather than polyplex structural alterations, providing a universal strategy to finely tune the mRNA multiorgan target.\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"33 1\",\"pages\":\"\"},\"PeriodicalIF\":16.0000,\"publicationDate\":\"2025-10-01\",\"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.5c12386\",\"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.5c12386","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}
Mass-Ratio-Controlled Organ-Selective Phosphatidyl Polymer Carrier for In Vivo Targeted mRNA Delivery.
Organ-selective mRNA transfection enables precise regulation of gene expression in specific tissues and represents a pivotal strategy for advancing mRNA therapeutics toward multiorgan and multi-indication applications. However, prevailing delivery systems rely on tissue-specific ligands or polyplex chemical modifications, limiting the modularity, scalability, and clinical translatability of delivery systems. Herein, we report a mass-ratio-controlled organ-selective (MACO) mRNA delivery platform based on phosphatidyl polyethylenimine derivatives (PEI-PPs). Impressively, the MACO platform enables precise and reversible switching of mRNA transfection among the spleen (94%), liver (78%), and lung (95%) by simply adjusting the mass ratio of PEI-PP to mRNA, without requiring additional targeting ligands, charge modifiers, or chemical modifications. Mechanistic investigations revealed that varying mass ratios generate polyplexes with distinct surface charge and pKa profiles, which in turn adsorb plasma protein coronas forming specific "protein fingerprints" that mediate organ-selective capability. The MACO mechanism represents the demonstration of organ-selective mRNA delivery governed solely by formulation parameters rather than polyplex structural alterations, providing a universal strategy to finely tune the mRNA multiorgan target.
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.