{"title":"芬顿反应介导的内溶酶体破坏对有效的细胞质蛋白递送。","authors":"Peng Zhang,Qi Yao,Xiaonong Zhang,Xuan Yi,Chunsheng Xiao,Xuesi Chen","doi":"10.1021/acsnano.5c01922","DOIUrl":null,"url":null,"abstract":"Endolysosomal entrapment is still the major obstacle in cytosolic protein delivery. Methods that can efficiently promote endolysosomal escape are thus highly demanded. Herein, the possibility of transferring proteins from endolysosomes into the cytosol by Fenton reaction-mediated endolysosomal disruption was examined. Proteins and iron ions were loaded in calcium carbonate nanoparticles, and the intracellular distribution and bioactivities of proteins after cellular uptake were analyzed. This technology, termed chemodynamic internalization (CDI), was found to efficiently deliver various proteins, including ribonuclease A, green fluorescent protein, β-galactosidase, and horseradish peroxidase, into the cytosol by mitochondrial calcium overload-enhanced Fenton reaction-mediated lipid peroxidation and ensuing rupture of endolysosomal membranes, maintaining the bioactivity of delivered proteins. Therefore, CDI provides an efficient and general tool for cytosolic protein delivery and may advance protein-related basic research and drug development.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"3 1","pages":""},"PeriodicalIF":16.0000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fenton Reaction-Mediated Endolysosomal Disruption for Efficient Cytosolic Protein Delivery.\",\"authors\":\"Peng Zhang,Qi Yao,Xiaonong Zhang,Xuan Yi,Chunsheng Xiao,Xuesi Chen\",\"doi\":\"10.1021/acsnano.5c01922\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Endolysosomal entrapment is still the major obstacle in cytosolic protein delivery. Methods that can efficiently promote endolysosomal escape are thus highly demanded. Herein, the possibility of transferring proteins from endolysosomes into the cytosol by Fenton reaction-mediated endolysosomal disruption was examined. Proteins and iron ions were loaded in calcium carbonate nanoparticles, and the intracellular distribution and bioactivities of proteins after cellular uptake were analyzed. This technology, termed chemodynamic internalization (CDI), was found to efficiently deliver various proteins, including ribonuclease A, green fluorescent protein, β-galactosidase, and horseradish peroxidase, into the cytosol by mitochondrial calcium overload-enhanced Fenton reaction-mediated lipid peroxidation and ensuing rupture of endolysosomal membranes, maintaining the bioactivity of delivered proteins. Therefore, CDI provides an efficient and general tool for cytosolic protein delivery and may advance protein-related basic research and drug development.\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"3 1\",\"pages\":\"\"},\"PeriodicalIF\":16.0000,\"publicationDate\":\"2025-09-25\",\"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.5c01922\",\"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.5c01922","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}
Fenton Reaction-Mediated Endolysosomal Disruption for Efficient Cytosolic Protein Delivery.
Endolysosomal entrapment is still the major obstacle in cytosolic protein delivery. Methods that can efficiently promote endolysosomal escape are thus highly demanded. Herein, the possibility of transferring proteins from endolysosomes into the cytosol by Fenton reaction-mediated endolysosomal disruption was examined. Proteins and iron ions were loaded in calcium carbonate nanoparticles, and the intracellular distribution and bioactivities of proteins after cellular uptake were analyzed. This technology, termed chemodynamic internalization (CDI), was found to efficiently deliver various proteins, including ribonuclease A, green fluorescent protein, β-galactosidase, and horseradish peroxidase, into the cytosol by mitochondrial calcium overload-enhanced Fenton reaction-mediated lipid peroxidation and ensuing rupture of endolysosomal membranes, maintaining the bioactivity of delivered proteins. Therefore, CDI provides an efficient and general tool for cytosolic protein delivery and may advance protein-related basic research and drug development.
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.