Department of Chemistry, University of Central Florida, P.O. Box 162366, Orlando, Florida 32816, USA.
J Am Chem Soc. 2013 Feb 13;135(6):2112-5. doi: 10.1021/ja3122312. Epub 2013 Jan 30.
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.
单线态氧敏化光动力疗法（PDT）依赖于待治疗组织中的氧气浓度。然而，大多数癌症病变的血管系统较差，因此处于缺氧状态，这极大地阻碍了 PDT 的疗效。一种不依赖于氧气的 PDT 方法可能会规避这一限制。为了解决这个问题，我们制备了硫鎓盐，通过在细胞质内产生光酸，在 HCT 116 细胞内引起 pH 值下降。这个过程是通过内吞的光酸生成剂（PAG）的单光子或双光子吸收（1PA 或 2PA）驱动的。这些 PAG 中的一种，其暗毒性显著降低，并且在生成光酸方面更有效，有效地诱导了 HCT 116 细胞的坏死性细胞死亡。数据表明，PAG 可能是一种有吸引力的 PDT 替代方式，可选择性地诱导缺氧组织（如肿瘤）中的细胞死亡。
