Photodynamic therapy (PDT) is an attractive alternative for the treatment of certain cancers as the conventional therapies, such as chemotherapy and radiation therapy, show many side-effects and some cancers are refractory to these modalities. PDT utilizes a special drug, classified as a photo-sensitizer (PS), which can be activated with light in the presence of oxygen to become a powerful anticancer agent. The cytotoxic effect results from the generation of singlet oxygen (and other reactive oxygen species (ROS)) in regions where only the PS, light, and oxygen overlap, but PDT has also been shown to have farther-reaching immune-triggered abscopal effects. There is ongoing interest in developing next-generation PSs that can exert similar light-driven anticancer effects but without the need for oxygen since some of the most aggressive and drug-resistant tumors are hypoxic. We are particularly focused on developing Ru- and Os-based PSs, where we can access a variety of excited states (with distinct properties and reactivities) by altering the ligand combinations around the metal center. Our TLD1433, a Ru-based metallodrug, is but one example and is currently in Phase II clinical trials for treating bladder cancer. TLD1433 and other Ru and Os-based PSs we have developed display possible modes of action that extend beyond ROS. Herein, we will discuss some of these possibilities that may contribute to their light-driven antitumor effects.

Exploring the mechanistic possibilities for light-responsive metallodrugs for cancer therapy

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.