Photodynamic Therapy (PDT) is a clinically-approved cancer treatment that utilizes a small-molecule photosensitizer (PS), light and endogenous molecular oxygen to produce cytotoxic reactive oxygen species (ROS) to promote cell death. PDT is advantageous over traditional cancer therapies (e.g. chemotherapy and radiation) as it uses low-energy visible light for destruction of tumors, while their inherent fluorescent properties make them useful for cancer diagnostic imaging and real-time fluorescence-guided surgery. However, lack of cancer cell selectivity and non-specific localization limits the success of current photosensitizers for cancer treatment, due to destruction of surrounding healthy cells causing adverse patient side effects.To overcome this issue, we describe the design, synthesis and characterization of an activatable photosensitizer (aPS) whereby in addition to light, activation of the PS is dependent on the over-active redox control system found in cancer cells. Our probe consists of the PS, protoporphyrin IX, and the FRET-based quencher dye, BHQ-3, conjugated on a linear disulfide scaffold. The close proximity of BHQ-3 to protoporphyrin IX quenches its fluorescence and ability to produce reactive oxygen species. Upon enzymatic (e.g. Thioredoxin) or non-enzymatic (e.g. Glutathione) thiol-mediated disulfide reduction, liberation of the photosensitizer from the quencher restores its native properties and enables selective destruction of cancer cells. We have demonstrated the probe’s ability to be activated in cancer cells in a thiol-dependent manner and can be used to destroy breast and lung cancer cells upon low-energy red-light irradiation.

Exploiting the cellular redox control system for activatable Photodynamic Therapy

2019 Spring National Meeting

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