Ge Shi / Chemistry & Biochemistry / Faculty Mentor: Sherri McFarland
Tumor hypoxia presents a major challenge in cancer therapy. Hypoxia can disrupt drug uptake and function, and induce other cellular adaptations that render treatment ineffective. Treatment modalities such as photodynamic therapy (PDT) are particularly susceptible to hypoxia since the antitumor effects of PDT rely primarily on the sensitization of singlet oxygen and other reactive oxygen species (ROS). There is ongoing interest in equipping photosensitizers with alternate modes of action to complement the PDT pathway in hypoxia. Recent research has been focused on developing light-responsive compounds that exploit oxygen-independent phototoxic pathways for treating some of the most aggressive and drug-resistant tumors. Herein we will introduce our work on the development of transition metal complexes as photosensitizers for PDT that have the potential to exploit alternate modes of action. We present our proof-of-concept strategies for achieving in vitro photocytotoxicity in both normoxia and hypoxia with such light-triggered metallodrugs, with emphasis on the metal-ligand combinations.
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