title: Preparation of a camptothecin prodrug with glutathione-responsive disulfide linker for anticancer drug delivery.
abstract: We present here a novel camptothecin (CPT) prodrug based on polyethylene glycol monomethyl ether-block-poly(2-methacryl ester hydroxyethyl disulfide-graft-CPT) (MPEG-SS-PCPT). It formed biocompatible nanoparticles (NPs) with diameters of approximately 122 nm with a CPT loading content as high as approximately 25 wt% in aqueous solution. In in vitro release studies, these MPEG-SS-PCPT NPs could undergo triggered disassembly and much faster release of CPT under glutathione (GSH) stimulus than in the absence of GSH. The CPT prodrug had high antitumor activity, and another anticancer drug, doxorubicin hydrochloride (DOX⋅HCl), could also be introduced into the prodrug with a high loading amount. The DOX·HCl-loaded CPT prodrug could deliver two anticancer drugs at the same time to produce a collaborative cytotoxicity toward cancer cells, which suggested that this GSH-responsive NP system might become a promising carrier to improve drug-delivery efficacy.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000 (P.R. China), Fax: (+86) 931-8912582; School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457 (Singapore).
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xu
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Xu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004220:Disulfides; D011355:Prodrugs; D004317:Doxorubicin; D005978:Glutathione; D002166:Camptothecin
keywords: cancer; cytotoxicity; disulfides; drug delivery; drug design