title: Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging.
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 potentialin 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.
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Jay
authors.initials: J
authors.lastname: Lubow
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.affiliation: Beckman Research Institute, California Institute of Technology, Pasadena, CA ; Department of Chemistry, Technion-Israel Institute of Technology, Haifa.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Gross
authors.affiliation: Beckman Research Institute, California Institute of Technology, Pasadena, CA.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA ; Spectral Molecular Imaging, Inc., Beverly Hills CA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Farkas
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA ; Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
authors.forename: Lali K
authors.initials: LK
authors.lastname: Medina-Kauwe
keywords: Multimode optical imaging; fluorescence lifetime imaging; photosensitizers; spectral imaging; targeted gallium corrole