Triarylsulfonium salts, pioneered by James V. Crivello, have impacted numerous fields ranging from photocured coatings to high resolution photoresists used in integrated circuit chip manufacturing. The impact of these materials is now extending into intriguing new frontiers in biomedical research. Singlet oxygen sensitized photodynamic therapy (PDT) relies on the concentration of oxygen of the tissue that is to be treated. Most cancer lesions, however, have poor vasculature and are hypoxic as a result. This significantly hinders PDT efficacies. We demonstrated that customized sufonium salts produce a pH drop within HCT 116 cells via the generation of photoacid within the cytosol, likely beginning in the lysosomes. This process was driven by one- or two-photon absorption of the endocytosed photoacid generators (PAGs) and is oxygen-independent. One of our PAGs, that had a significantly lower dark cytotoxicity and was more efficient in generating photoacid, effectively induced necrotic cell death in HCT 116 cells upon photoexcitation. These results suggest that PAGs may be an attractive alternative PDT modality to selectively induce cell death in oxygen-deprived tissue such as tumors.

Triarylsulfonium salt-based photodynamic therapy: A new paradigm in cancer treatment

248th National Meeting (2014)

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