Hydroxy-corrole and its gallium(III) complex as new photosensitizer for photodynamic therapy against breast carcinoma

作者：Sun, Yan-Mei; Jiang, Xiao; Liu, Ze-Yu; Liu, Ling-Gui; Liao, Yu-Hui^*; Zeng, Lei; Ye, Yong; Liu, Hai-Yang^*

来源：European Journal of Medicinal Chemistry, 2020, 208: 112794.

DOI：10.1016/j.ejmech.2020.112794

• Corrole
• Gallium(III) complex
• Photosensitizer
• Photodynamic therapy
• Breast carcinoma

Three mono-hydroxy corroles 1-3 and their gallium(III) complexes Ga1-3 were synthesized, and their photodynamic antitumour activities towards breast cancer cells were investigated. All corroles showed excellent cytotoxicity against the MDA-MB-231 and 4T1 cell lines upon light irradiation at 625 nm. Ga3 exhibited excellent phototoxicity and selectivity against MDA-MB-231 cells, with an IC50 of 0.06 +/- 0.03 mu M and a selective index value of 1338.83 (relative to human normal Huvec cells). The performance of Ga3 was even better than that of the clinical photodynamic therapy drug m-THPC. A preliminary mechanistic investigation revealed that corrole 3 and Ga3 were mainly located in the cytoplasm. Upon irradiation, they could generate intracellular reactive oxygen to destroy the mitochondrial membrane potential and arrest the cell cycle at the sub-G1 phase. Flow cytometry revealed that corrole 3 and Ga3 induced cancer cell apoptosis after photodynamic treatment. Corrole 3 and Ga3 displayed negligible cytotoxicity in the dark. These results suggest that corrole 3 and Ga3 are promising candidates for use in the photodynamic therapy of breast cancer.

• 单位
  广州军区广州总医院; 南方医科大学