Illuminating the future: a review of ruthenium-based agents for dual action photochemotherapy and photodynamic therapy

Platnium-based chemotherapeutics are now being used to treat ∼50% of human cancers, leading to the investigation of other metal-based chemotherapeutics, including ruthenium. Due to their rich photophysical and biological properties, Ru(ii) polypyridyl complexes have been developed as potential photoactivated chemotherapeutics. TLD-1433 is a Ru(ii)-based photosensitizer that utlizes photodynamic therapy (PDT) currently in phase II human clinical trials for the treatment of non-muscle invasive bladder cancer. PDT involves irradiation of a photosensitizer to generate reactive oxygen species (ROS) that cause oxidative damage to induce cancer cell death. Another photoactivated strategy is photoactivated chemotherapy (PCT), which involves a biologically inert photocage that releases labile ligands or biologically active compounds upon irradiation. Both strategies are advantageous and offer spatiotemporal control of oxidative damage or the photorelease of a therapeutic compound. Since the development of the first dual-action PDT/PCT agent by the Turro group, improved compounds of this class of agents were designed with increased molar absorptivity and longer wavelength absorption maxima, and to target enzymes upregulated in disease states as discussed in this review.