Counterion Tuning of Near-Infrared Organic Salts Dictates Phototoxicity to Inhibit Tumor Growth.

ABSTRACT: Photodynamic therapy (PDT) has the potential to improve cancer treatment by providing dual selectivity through the use of both photoactive agent and light, with the goal of minimal harmful effects from either the agent or light alone. However, current PDT is limited by insufficient photosensitizers (PSs) that can suffer from low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), or undesirable cytotoxicity (toxicity without light irradiation). Recently, we reported a platform for decoupling optical and electronic properties with counterions that modulate frontier molecular orbital levels of a photoactive ion. Here, we demonstrate the utility of this platform in vivo by pairing near-infrared (NIR) photoactive heptamethine cyanine cation (Cy⁺), which has enhanced optical properties for deep tissue penetration, with counterions that make it cytotoxic, phototoxic, or nontoxic in a mouse model of breast cancer. We find that pairing Cy⁺ with weakly coordinating anion FPhB^- results in a selectively phototoxic PS (CyFPhB) that stops tumor growth in vivo with minimal side effects. This work provides proof of concept that our counterion pairing platform can be used to generate improved cancer PSs that are selectively phototoxic to tumors and nontoxic to normal healthy tissues.

SUBMITTER: Broadwater D 

PROVIDER: S-EPMC9743086 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature