Profiting from Light-Induced Metal-to-Metal Intramolecular Electron Transfer: Towards Highly Efficient Heterodinuclear Photosensitizers for Photodynamic Therapy

Abstract

Photodynamic therapy is receiving increasing attention due to its versatile application in anticancer therapy. Ru(II) and Pt(II) complexes are among the most investigated compounds as potential photosensitizers for photodynamic therapy based on their outstanding photophysical and biological properties (i.e., strong emission, high intersystem crossing efficiency, large Stokes shift, high (photo-)stability, biological compatibility, good water solubility). While these classes of compounds have been widely studied separately or combined in derivatives that display a dual therapeutic effect, herein, a novel study on the conjugation of Ru(II) and Pt(II) fragments into a single bimetallic conjugate is proposed. It is assumed that this molecular design could undergo an intramolecular electron transfer from the Ru(II) moiety to the Pt(II) moiety upon irradiation to produce a highly efficient excited state. Capitalizing on the presence of both metals, the bimetallic conjugate was found to generate singlet oxygen with an outstanding efficiency in comparison to its individual components. To enhance the pharmacological profile, the bimetallic complex was encapsulated into polymeric nanoparticles. The nanoparticles were demonstrated to eradicate human breast adenocarcinoma monolayer cells as well as multicellular tumor spheroids upon light irradiation at nanomolar concentrations. We are confident that this approach will open new avenues towards the development of novel highly efficient photosensitizers.