Ru(II) containing photosensitizers for photodynamic therapy: A critique on reporting and an attempt to compare efficacy

Ruthenium(II)-based coordination complexes have emerged as photosensitizers (PSs) for photodynamic therapy (PDT) in oncology as well as antimicrobial indications and have great potential. Their modular architectures that integrate multiple ligands can be exploited to tune cellular uptake and subcellular targeting, solubility, light absorption, and other photophysical properties. A wide range of Ru(II) containing compounds, as well as other coordination complexes, have been reported as PSs for PDT or as photochemotherapy (PCT) agents. Many studies employ a common scaffold that is subject to systematic variation in one or two ligands to elucidate the impact of these modifications on the photophysical and photobiological performance. Studies that probe the excited state energies and dynamics within these molecules are of fundamental interest and are used to design next-generation systems. However, a comparison of the PDT efficacy between Ru(II) containing PSs and 1st or 2nd generation PSs, already in clinical use or in preclinical/clinical studies, is rare. Even comparisons between Ru(II)-containing molecular structures are difficult, given the wide range of excitation wavelengths, power densities, and cell lines utilized. Despite this gap, PDT dose metrics to quantify PS efficacy are available to perform qualitative comparisons. Such models are independent of excitation wavelength and are based on common outcome metrics, such as the photon density absorbed by the Ru(II) compound to cause 50% cell kill (LD50) based on the previously established threshold model. In this focused photophysical review, we identified all published studies on Ru(II)-containing PSs since 2005 that reported the required photophysical, light treatment, and in vitro outcome data to permit the application of the Photodynamic Threshold Model to quantify their potential efficacy. The resulting LD50 values range from less than 10(13) to above 10(20) [hv cm(3)], indicating a wide range in PDT efficacy and required optical energy density for ultimate clinical translation. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Ruthenium(II)-based coordination complexes have great potential as photosensitizers for photodynamic therapy. The modular architectures of these complexes allow for tuning of various properties such as cellular uptake, subcellular targeting, solubility, and light absorption. Many studies focus on systematic variation of ligands to investigate their impact on photophysical and photobiological performance. However, comparisons between Ru(II)-based PSs and other generations of PSs are scarce. Nonetheless, quantitative models based on PDT dose metrics are available for qualitative comparisons. This review summarizes the relevant studies on Ru(II)-containing PSs and their potential efficacy.