The unique photophysical and biological properties of metal-based compounds have led to remarkable advances in their application across various cancer therapeutic and diagnostic modalities, including chemotherapy, photoactivated chemotherapy, photodynamic therapy, and diagnostic imaging. However, their exploration in photothermal therapy has been limited because their high-energy absorption characteristics favor radiative or energy transfer processes rather than nonradiative decay. Herein, two Ru(II) polypyridyl complexes, RuDA1 and RuDA2, employing narrow-band-gap donor-acceptor ligands, were designed and synthesized for photothermal therapy. Photophysical studies reveal that both complexes exhibit a low-energy absorption band in the near-infrared (NIR) region, which undergoes a pronounced redshift upon aggregation. Notably, the incorporation of two thiophene bridges in RuDA2 narrows the energy gap and enhances electronic nonadiabatic coupling. This structural modification facilitates a more efficient nonradiative relaxation process, resulting in a superior photothermal conversion efficiency of 51.3% compared to 39.3% for RuDA1. In vitro biological studies reveal that both RuDA1 and RuDA2 exhibit potent photothermal cytotoxicity, with RuDA2 showing particularly significant efficacy through mitochondrial targeting. This study demonstrates that rationally designed NIR-absorbing Ru(II) polypyridyl-based photothermal agents (PTAs) offer a robust platform for advancing photothermal therapy.
Huang et al. (Wed,) studied this question.