Preparation of a Camptothecin Prodrug with Glutathione‐Responsive Disulfide Linker for Anticancer Drug Delivery |
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| Authors: | Dr Zhigang Xu Dongdong Wang Shuang Xu Dr Xiaoyan Liu Prof?Dr Xiaoyu Zhang Prof?Dr Haixia Zhang |
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| Institution: | 1. State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000 (P.R. China), Fax: (+86)?931‐8912582;2. School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457 (Singapore);3. School of Basic Medical Science, Lanzhou University, Lanzhou 730000, (P.R. China) |
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| 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. |
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| Keywords: | cancer cytotoxicity disulfides drug delivery drug design |
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