Selective cell death by photochemically induced pH imbalance in cancer cells.
Singlet oxygen sensitized photodynamic therapy (PDT) relies on the concentration of oxygen in the tissue to be treated. Most cancer lesions, however, have poor vasculature and, as a result, are hypoxic, significantly hindering PDT efficacies. An oxygen-independent PDT method may circumvent this limitation. To address this, we prepared sulfonium salts that produced a pH drop within HCT 116 cells via the generation of a photoacid within the cytosol. This process was driven by one- or two-photon absorption (1PA or 2PA) of the endocytosed photoacid generators (PAGs). One of these PAGs, which had a significantly lower dark cytotoxicity and was more efficient in generating a photoacid, effectively induced necrotic cell death in the HCT 116 cells. The data suggest that PAGs may be an attractive alternative PDT modality to selectively induce cell death in oxygen-deprived tissue such as tumors.
Department of Chemistry, University of Central Florida, P.O. Box 162366, Orlando, Florida 32816, USA.
Xiling
X
Yue
Ciceron O
CO
Yanez
Sheng
S
Yao
Kevin D
KD
Belfield
D016923:Cell Death / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D055668:Photochemical Processes; D026082:Singlet Oxygen / Q000737:chemistry / Q000494:pharmacology*
D026082:Singlet Oxygen