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Proceedings Paper

Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging
Author(s): Jae Youn Hwang; Jay Lubow; David Chu; Zeev Gross; Harry B. Gray; Daniel L. Farkas; Lali K. Medina-Kauwe
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Paper 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.

Paper Details

Date Published: 17 February 2011
PDF: 6 pages
Proc. SPIE 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 78860M (17 February 2011); doi: 10.1117/12.873337
Show Author Affiliations
Jae Youn Hwang, Cedars-Sinai Medical Ctr. (United States)
Jay Lubow, Cedars-Sinai Medical Ctr. (United States)
David Chu, Cedars-Sinai Medical Ctr. (United States)
Zeev Gross, Beckman Research Institute, California Institute of Technology (United States)
Technion-Israel Institute of Technology (Israel)
Harry B. Gray, Beckman Research Institute, California Institute of Technology (United States)
Daniel L. Farkas, Univ. of Southern California (United States)
Spectral Molecular Imaging, Inc. (United States)
Lali K. Medina-Kauwe, Cedars-Sinai Medical Ctr. (United States)
Univ. of Southern California (United States)


Published in SPIE Proceedings Vol. 7886:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX
David H. Kessel; Tayyaba Hasan, Editor(s)

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