Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging

Jae Youn Hwang; Jay Lubow; David Chu; Zeev Gross; Harry B. Gray; Daniel L. Farkas; Lali K. Medina-Kauwe

doi:10.1117/12.873337

17 February 2011 Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging

Jae Youn Hwang, Jay Lubow, David Chu, Zeev Gross, Harry B. Gray, Daniel L. Farkas, Lali K. Medina-Kauwe

Author Affiliations +

Proceedings Volume 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX; 78860M (2011) https://doi.org/10.1117/12.873337
Event: SPIE BiOS, 2011, San Francisco, California, United States

Abstract

We recently developed a novel therapeutic particle, HerGa, for breast cancer treatment and detection. HerGa consists of a tumor-targeted cell penetration protein noncovalently assembled with a gallium-metallated corrole. The corrole is structurally similar to porphyrin, emits intense fluorescence, and has proven highly effective for breast tumor treatment preclinically, without light exposure. Here, we tested HerGa as a photosensitizer for photodynamic therapy and investigated its mechanism of action using multimode optical imaging. Using confocal fluorescence imaging, we observed that HerGa disrupts the mitochondrial membrane potential in situ, and this disruption is substantially augmented by light exposure. In addition, spectral and fluorescence lifetime imaging were utilized to both validate the mitochondrial membrane potential disruption and investigate HerGa internalization, allowing us to optimize the timing for light dosimetry. We observed, using advanced multimode optical imaging, that light at a specific wavelength promotes HerGa cytotoxicity, which is likely to cause disruption of mitochondrial function. Thus, we can identify for the first time the capacity of HerGa as a photosensitizer for photodynamic therapy and reveal its mechanism of action, opening possibilities for therapeutic intervention in human breast cancer management.

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Jae Youn Hwang, Jay Lubow, David Chu, Zeev Gross, Harry B. Gray, Daniel L. Farkas, and Lali K. Medina-Kauwe "Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging", Proc. SPIE 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 78860M (17 February 2011); https://doi.org/10.1117/12.873337

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