10.1021/acs.biomac.9b00367.s001 Xinyu Peng Xinyu Peng Qingqing Pan Qingqing Pan Boya Zhang Boya Zhang Shiyu Wan Shiyu Wan Sai Li Sai Li Kui Luo Kui Luo Yuji Pu Yuji Pu Bin He Bin He Highly Stable, Coordinated Polymeric Nanoparticles Loading Copper(II) Diethyldithiocarbamate for Combinational Chemo/Chemodynamic Therapy of Cancer American Chemical Society 2019 nanoparticle anticancer activity DSF vivo antitumor results PEC Cu anticancer mechanism studies drug loading contents 2019-05-22 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Highly_Stable_Coordinated_Polymeric_Nanoparticles_Loading_Copper_II_Diethyldithiocarbamate_for_Combinational_Chemo_Chemodynamic_Therapy_of_Cancer/8204150 Disulfiram (DSF) has excellent <i>in vitro</i> anticancer activity in the presence of Cu­(II). The anticancer mechanism studies have demonstrated that copper­(II) diethyldithiocarbamate, Cu­(DDC)<sub>2</sub>, 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)-<i>b</i>-poly­(ester-carbonate) (PEC) for efficient loading of Cu­(DDC)<sub>2</sub>, which was generated by the <i>in situ</i> 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. <i>In vitro</i> anticancer study established that Cu­(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu­(DDC)<sub>2</sub>-based chemotherapy and chemodynamic therapy mediated by bioavailable Cu­(II) that was not in the form of Cu­(DDC)<sub>2</sub>. The <i>in vivo</i> 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.