Disulfiram (DSF), an alcohol-aversion drug, has been explored for cancer treatment. Copper diethyldithiocarbamate (Cu(DDC)2) complex formed by DSF and copper ions is a major active ingredient for its anticancer activity. Direct administration of Cu(DDC)2 is a promising strategy to enhance the anticancer efficacy of DSF. However, efficient drug delivery remains a significant challenge for Cu(DDC)2 and hinders its clinical use. In this study, we developed a facile Stabilized Metal Ion Ligand complex (SMILE) method to prepare Cu(DDC)2 nanoparticles (NPs). The SMILE method could prepare Cu(DDC)2 NPs with different types of stabilizers including 1, 2-distearoyl-sn-glycerol-3-phosphoethanolamine-poly(ethylene glycol) 2000 (DSPE-PEG), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), methoxy poly(ethylene glycol) 5000 -b-poly(L-lactide) 5000 (PEG-PLA), and other generally recognized as safe (GRAS) excipients approved by the US Food and Drug Administration (FDA) . The optimized formulations demonstrated excellent drug loading efficiency (close to 100%), high drug concentrations (increased drug concentration by over 200-fold compared to the traditional micelle formulation), and an optimal particle size in the sub-100 nm range. The anticancer effects of Cu(DDC)2 NP formulations were determined by multiple assays including MTT Assay, Colony-forming Assay, Calcein-AM/Propidium Iodide (PI) Staining, and others. Cu(DDC)2 NPs showed excellent activity against drug-resistant prostate cancer cells and other cancer cells. To our best knowledge, the SMILE method provides, for the first time, a simple yet efficient process for generating Cu(DDC)2 NPs with high drug concentration, excellent loading efficiency, and desirable physicochemical properties. This method could potentially address drug delivery challenges of DSF/Copper based chemotherapy and facilitate its clinical translation.

Disulfiram copper nanoparticles prepared with a Stabilized Metal Ion Ligand Complex (SMILE) method for cancers treatment

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.