Supramolecular Assembly of an Organoplatinum(II) Complex Boosts Intersystem Crossing for Potentiated Photocatalytic Therapy and Disulfidptosis

Abstract

The supramolecular assembly of platinum(II) terpyridine complexes, driven by noncovalent Pt(II)•••Pt(II) metallophilic interactions and π-π stacking, has been demonstrated to exhibit significant potential for advanced applications. In this study, we present PtATPA, an organoplatinum(II) complex with an electron-donor-acceptor structure that self-assembles into nanostructures through Pt•••Pt and π-π interactions, exhibiting enhanced photophysical properties for improved photocatalytic therapy (PCT). The assembly induces a significantly improved singlet-triplet intersystem crossing, thereby amplifying the PCT effect. Upon white light irradiation, PtATPA complex not only generates a substantial amount of reactive oxygen species (ROS) but also photocatalyzes the oxidation of nicotinamide adenine dinucleotide phosphate (NADPH)-an essential coenzyme.In A549 cells, PtATPA-induced oxidative stress downregulates GLUT1 to disrupt glucose metabolism, leading to NADPH depletion, disulfide stress, F-actin cytoskeleton collapse, and ultimately disulfidptosis. This study provides a promising strategy for leveraging self-assembled metal complexes to improve PCT and induce tumorspecific disulfidptosis, offering new insights for future cancer therapy.