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 limi...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2013-02, Vol.135 (6), p.2112-2115
Main Authors: Yue, Xiling, Yanez, Ciceron O, Yao, Sheng, Belfield, Kevin D
Format: Article
Language:English
Subjects:
Cell Death - drug effects
HCT116 Cells
Humans
Hydrogen-Ion Concentration
Molecular Structure
Photochemical Processes
Singlet Oxygen - chemistry
Singlet Oxygen - pharmacology
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja3122312