title: Triple Redox Responsive Poly(Ethylene Glycol)-Polycaprolactone Polymeric Nanocarriers for Fine-Controlled Drug Release.
abstract: Stimuli-responsive nanocarriers with the ability to respond to tumorous heterogeneity have been extensively developed for drug delivery. However, the premature release during blood circulation and insufficient intracellular drug release are still a significant issue. Herein, three disulfide bonds are introduced into the amphiphilic poly(ethylene glycol)-polycaprolactone copolymer blocks to form triple-sensitive cleavable polymeric nanocarrier (tri-PESC NPs) to improve its sensitivity to narrow glutathione (GSH) concentration. The tri-PESC NPs keep intact during blood circulation due to the limited cleaving of triple-disulfide bonds, whereas the loaded drug is efficiently released at tumor cells with the increased concentration of GSH. In vitro studies of doxorubicin-loaded tri-PESC NPs show that the nanocarriers achieve sufficient drug release in cancerous cells and inhibit the tumor cells growth, though they only bring minimum damage to normal cells. Therefore, the tri-PESC NPs with triple-sensitive cleavable bonds hold great promise to improve the therapeutic index in cancer therapy.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Caiyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Leihou
authors.initials: L
authors.lastname: Shao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Lu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.|College of Science, Beijing University of Chemical Technology, Beijing, 100029, China.
authors.forename: Chenying
authors.initials: C
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.|College of Science, Beijing University of Chemical Technology, Beijing, 100029, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wei
authors.affiliation: The First Affiliated Hospital of Jiamusi University, Jiamusi, 154003, China.
authors.forename: Junxing
authors.initials: J
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Jiamusi University, Jiamusi, 154003, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D055672:Static Electricity
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: poly(ethylene glycol)-polycaprolactone; stimuli-responsive drug delivery; triple-disulfide bond