Complex of Cisplatin with Biocompatible Poly(ethylene glycol) with Pendant Carboxyl Groups for the Effective Treatment of Liver Cancer

Cisplatin was incorporated into polymeric carriers through the coordination of Pt with the carboxylic groups of methoxypoly( ethylene glycol) (mPEG)-block-poly[(2-carboxy-ethylsulfanyl)-propyl glycidyl ether] (PCPGE). The mPEG-b-PCPGE/Pt complexes with a Pt content of 14 wt % could self-assemble into spheric micelles with diameter of about 80 nm in aqueous solution. The effective internalization of the polymer platinum micelles by the cells via an endocytosis mechanism was confirmed by confocal laser scanning microscopy and flow cytometry. The antitumor activity of the polymeric micelles was similar to that of cisplatin in vitro. The in vivo blood clearance of platinum was studied, and the results show that the micelles exhibited longer blood circulation than the free cisplatin. The biodistribution of cisplatin and its micelles in mice was studied through the measurement of the Pt content in plasma, organs, and tumors, especially in tumor cell DNA. Their antitumor activity in vivo, assessed in mice bearing H22 liver cancers, showed that the micelles exhibited greater antitumor efficacy than free cisplatin. Therefore, this polymer platinum micelle is a promising candidate as a smart antitumor drug carrier for malignancy therapy in future clinical applications. (C) 2014 Wiley Periodicals, Inc