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 122nm with a CPT loading content as high as approximately 25wt% 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 (DOXHCl), could also be introduced into the prodrug with a high loading amount. The DOXHCl-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.