{"title":"Dual Reduction-Sensitive Nanomicelles for Antitumor Drug Delivery with Low Toxicity to Normal Cells","authors":"Shixi Li, Xue Liu, Xuhua Liang, Xuejun Wang","doi":"10.1021/acsanm.4c01908","DOIUrl":null,"url":null,"abstract":"In this work, a dual-thiol-responsive drug delivery system was fabricated by embedding the reduction-sensitive doxorubicin prodrug (DOX-prodrug) in the reduction-responsive carrier. Therefore, the amphiphilic block copolymer poly(lactide)-SS-poly(2-hydroxyethyl methacrylate) (PLA-SS-PHEMA) was synthesized to be used as an anticancer drug carrier, which would self-assemble into spherical micelles in an aqueous solution with an average diameter of approximately 100 nm. The DOX-prodrug could be loaded into the PLA-SS-PHEMA micelles with a high drug loading efficiency (5.27%) and entrapment efficiency (58%). The in vitro release results demonstrated that the cleavage of the intervening disulfide bonds in both the carrier and prodrug in response to a reductive environment led to fast release of the anticancer drug. The cytotoxicity results showed that the dual reduction-sensitive drug delivery system could effectively inhibit tumor cell proliferation, while it had almost no side effects on normal cells. The CLSM results are in agreement with that of flow cytometry, indicating that the drug-loaded micelles could be efficiently internalized into the HeLa cells and the drug is released into the cytoplasm and then enters the nuclei. We further investigated the cell endocytosis mechanism for the micelles, suggesting that the clathrin-mediated endocytosis pathway played the main role in the internalization of this nanocarrier.","PeriodicalId":6,"journal":{"name":"ACS Applied Nano Materials","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Nano Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsanm.4c01908","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
In this work, a dual-thiol-responsive drug delivery system was fabricated by embedding the reduction-sensitive doxorubicin prodrug (DOX-prodrug) in the reduction-responsive carrier. Therefore, the amphiphilic block copolymer poly(lactide)-SS-poly(2-hydroxyethyl methacrylate) (PLA-SS-PHEMA) was synthesized to be used as an anticancer drug carrier, which would self-assemble into spherical micelles in an aqueous solution with an average diameter of approximately 100 nm. The DOX-prodrug could be loaded into the PLA-SS-PHEMA micelles with a high drug loading efficiency (5.27%) and entrapment efficiency (58%). The in vitro release results demonstrated that the cleavage of the intervening disulfide bonds in both the carrier and prodrug in response to a reductive environment led to fast release of the anticancer drug. The cytotoxicity results showed that the dual reduction-sensitive drug delivery system could effectively inhibit tumor cell proliferation, while it had almost no side effects on normal cells. The CLSM results are in agreement with that of flow cytometry, indicating that the drug-loaded micelles could be efficiently internalized into the HeLa cells and the drug is released into the cytoplasm and then enters the nuclei. We further investigated the cell endocytosis mechanism for the micelles, suggesting that the clathrin-mediated endocytosis pathway played the main role in the internalization of this nanocarrier.
期刊介绍:
ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.