Copper (alpha)/cis-platinum-loaded nanogels as an adjuvant potentiate disulfiram's antitumor efficacy

Disulfiram (DSF) is nontoxic and exerts anticancer activity by forming highly toxic chelates via its metabolite diethyldithiocarbamate with transition metal ions. However, there are not enough such ions in the human body to maintain the therapeutic effect. Herein, we report nanogels that complex copper ions or cis-platinum (CDDP) for tumor metal delivery to potentiate DSF's antitumor efficacy. We synthesized zwitterionic poly[N-(3-(methacryloyloxy-2-hydroxy)propyl)]-N-methyl glycine (PGMA-SAR) capable of chelating copper ions or CDDP and formed nanogels with suitable size and zeta potential. The intravenously injected nanogels circulated long in the blood compartment and delivered a high concentration of metal ions to the tumor. Separately administered DSF could sequester the metal ions from the nanogels and form highly cytotoxic complexes with potent in vitro and in vivo anticancer activity. This study provides a new strategy to potentiate DSF in anticancer treatment.

Automated summary

This study presents a new strategy to enhance the anticancer activity of disulfiram (DSF) by using nanogels to deliver metal ions to tumors. The nanogels, developed with the ability to chelate copper ions or cis-platinum (CDDP), effectively delivered a high concentration of metal ions to the tumor, resulting in potent in vitro and in vivo anticancer activity of separately administered DSF.