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

机译:使用多模光学成像研究目标镓的光敏剂电位

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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.
机译:我们最近开发了一种用于乳腺癌治疗和检测的新型治疗性颗粒HerGa。 HerGa由靶向肿瘤的细胞渗透蛋白组成,该蛋白与镓金属化的金属化物非共价组装。该分子在结构上与卟啉相似,发出强烈的荧光,并且已被证明对临床前的乳癌治疗非常有效,并且没有光照。在这里,我们测试了HerGa作为光动力疗法的光敏剂,并使用多模光学成像技术研究了其作用机理。使用共聚焦荧光成像,我们观察到HerGa可以原位破坏线粒体膜电位,并且这种暴露在光线照射下会大大增强。另外,利用光谱和荧光寿命成像来验证线粒体膜电位破坏并研究HerGa内在化,从而使我们能够优化光剂量测定的时间。我们使用先进的多模光学成像技术观察到,特定波长的光会促进HerGa细胞毒性,这很可能导致线粒体功能中断。因此,我们可以首次确定HerGa作为光敏疗法的光敏剂的能力,并揭示其作用机理,为人类乳腺癌管理中的治疗干预打开了可能性。

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