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.
Keywords: Multimode optical imaging; fluorescence lifetime imaging; photosensitizers; spectral imaging; targeted gallium corrole.