Pt(IV) prodrug-gating MOF incorporating copper peroxide and ruthenium complex for NIR-mediated synergistic anticancer therapy

Abstract

The development of efficient and multifunctional nanosystems is crucial for enhancing anticancer therapy. The incorporation of therapeutic agents in nanocarriers often results in premature drug release, leading to unsatisfactory therapeutic effects. To overcome these challenges, a nanosystem MOF@Cu/Ru/Pt (MOF = metal-organic framework UiO-67(bpy), bpy = bipyridine, Cu = copper peroxide, Ru = [Ru(bpy)₃]²⁺, and Pt = Pt(IV) prodrug) is synthesized. The chemotherapeutic Pt(IV) prodrug can coordinate with MOF and act as a gating agent for the confinement and the glutathione-responsive controlled release of Cu and Ru species, respectively, for chemodynamic/photothermal and photodynamic therapies. Upon exposure to near-infrared irradiation, this material facilitates the enhanced generation of reactive oxygen species and a temperature rise. The in vitro studies of MOF@Cu/Ru/Pt demonstrate excellent biocompatibility in normal cells and remarkable therapeutic efficacy in 4T1 cancer cells, attributed to the synergistic anticancer effects.