In situ activatable Disulfiram-Rhodium(III) nanocomplex for Cu chelation and STAT3 inhibition to Potentiate photodynamic and immunotherapy

Abstract

Disulfiram (DSF) has gained interest for its anti-cancer potential, but its clinical application is hindered by its poor solubility, short half-life, and lack of tumor targeting. Nanotechnology has been employed to address these challenges, with various strategies developed for DSF delivery. However, these methods face issues such as low drug loading and complex synthesis. We present an in situ activatable Disulfiram-Rhodium (III) nanocomplex that surmounts these obstacles. Our nanocomplex self-assembles DSF with Rhodium (III) complexes, offering high drug loading, tumor microenvironment activation, and copper ion chelation. It also inhibits the STAT3 pathway, activating the immune environment and enhancing the anti-tumor immune response. Additionally, loading with Ce6 potentiates photodynamic and immunotherapy, providing synergistic effects. This novel nanocomplex holds promise for improved cancer treatment through enhanced targeting, activation, and therapeutic synergy.