Highly Stable, Coordinated Polymeric Nanoparticles Loading Copper(II) Diethyldithiocarbamate for Combinational Chemo/Chemodynamic Therapy of Cancer

Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu­(II). The anticancer mechanism studies have demonstrated that copper­(II) diethyldithiocarbamate, Cu­(DDC)2, is the crucial DSF’s metabolite exhibiting anticancer activity. In this paper, highly stable polymeric nanoparticles were fabricated via a coordination strategy between Cu­(II) and carboxylic groups in poly­(ethylene glycol)-b-poly­(ester-carbonate) (PEC) for efficient loading of Cu­(DDC)2, which was generated by the in situ reaction of DSF and Cu­(II). The properties of nanoparticles such as drug loading contents, sizes, and morphologies could be tuned by varying the feeding ratios of DSF, Cu­(II), and PEC. These Cu­(II)/DDC-loaded nanoparticles showed excellent stability in both neutral and weak acidic solutions and under dilution. In vitro anticancer study established that Cu­(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu­(DDC)2-based chemotherapy and chemodynamic therapy mediated by bioavailable Cu­(II) that was not in the form of Cu­(DDC)2. The in vivo antitumor results demonstrated that the Cu­(II)/DDC-loaded nanoparticles showed superior antitumor efficacy to DSF/Cu­(II). Our study provided a facile and effective strategy of highly stable coordination-mediated polymeric nanoparticles for combinational therapy of cancer.