Preparation of a camptothecin prodrug with glutathione-responsive disulfide linker for anticancer drug delivery.
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.
['Xu|Zhigang|Z|', 'Wang|Dongdong|D|', 'Xu|Shuang|S|', 'Liu|Xiaoyan|X|', 'Zhang|Xiaoyu|X|', 'Zhang|Haixia|H|']
D000818:Animals D000970:Antineoplastic Agents D001672:Biocompatible Materials D002166:Camptothecin D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D004220:Disulfides D004305:Dose-Response Relationship, Drug D004317:Doxorubicin D016503:Drug Delivery Systems D004354:Drug Screening Assays, Antitumor D005978:Glutathione D006801:Humans D015394:Molecular Structure D053758:Nanoparticles D010316:Particle Size D011355:Prodrugs D051381:Rats D013329:Structure-Activity Relationship D013499:Surface Properties
disulfides drug delivery cytotoxicity cancer drug design