Next-Generation Photosensitizers: Cyanine-Carborane Salts for Superior Photodynamic Therapy of Metastatic Cancer

Photodynamic therapy (PDT) has emerged as a promising targeted treatment for cancer. However, current PDT is limited by low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), and undesirable cytotoxicity (toxicity without light irradiation). Here, we report the discovery of cyanine-carborane salts as potent photosensitizers (PSs) that harness the near-infrared (NIR) absorbing [cyanine⁺] with the inertness of [carborane⁻]. The implementation of [cyanine⁺] [carborane⁻] salts dramatically enhance cancer targeting of the PSs and decrease cytotoxicity. We characterize the cellular uptake of the cyanine-carborane PSs, organelle localization, generation of reactive oxygen species (ROS) with the ability to cogenerate multiple ROS species, suppression of pro-metastatic pathways, and activation of apoptotic pathways. We further demonstrate the ability of optimized PSs to eliminate tumors in vivo using an orthotopic mouse model of breast cancer. These newly developed [cyanine⁺] [carborane⁻] salt PSs introduce a potent therapeutic approach against aggressive breast cancer while decreasing side effects.