Luminescent and photofunctional transition metal complexes for targeted cancer phototheranostics

Cancer poses a significant global health challenge, with high mortality rates underscoring the urgent need for more effective treatment strategies. Theranostics, which integrate therapeutic modalities with medical imaging into a single platform, offer a promising approach to enhance treatment precision and monitor therapeutic response in real time. Among various theranostic approaches, phototheranostics that combine light-activated therapeutic and diagnostic modalities are of particular interest due to their minimal invasiveness, high spatiotemporal control, and low systemic toxicity. Luminescent and photofunctional transition metal complexes are attractive candidates as phototheranostics due to their environment-sensitive and long-lived emission, efficient reactive oxygen species (ROS) photosensitization, and high photostability. In this chapter, we summarize our recent progress in the development of luminescent and photofunctional transition metal complexes as targeted cancer phototheranostics. We focus on the strategic designs of transition metal complexes as: (1) bioconjugation reagents that can be readily used to modify peptides and proteins with targeting capabilities; (2) stimuli-responsive agents that display emission turn-on and ROS generation in response to endogenous or exogenous stimuli; and (3) bioorthogonal reagents that enable targeted accumulation and activation through specific ligation or cleavage reactions. We also discuss current challenges and future perspectives on these complexes as phototheranostics, outlining a roadmap toward their clinical translation for cancer diagnosis and treatment. © 2025 Published by Elsevier Ltd.