Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity

• DOI: 10.1016/j.jconrel.2012.09.015
• Publication Date: 2012-10-04T19:02:13Z
• Authors: Jae Youn Hwang; David J. Lubow; David Chu; Jessica Sims; Felix Alonso-Vale...; Harry B. Gray; Zeev Gross; Daniel L. Farkas; Lali K. Medina-Kauwe
• Keywords: Photoexcitation; Membrane Potential, Mitochondrial; A sulfonated gallium(III) corrole; Porphyrins; Light; Singlet Oxygen; Singlet oxygen; Cell Survival; 500; Cytochromes c; Antineoplastic Agents; 01 natural sciences; Mitochondria; 0104 chemical sciences; Tumor targeting; Cell Line, Tumor; Neoplasms; Drug delivery; Humans; Nanoparticles

The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.