Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
J Control Release. 2012 Nov 10;163(3):368-73. doi: 10.1016/j.jconrel.2012.09.015. Epub 2012 Oct 4.
The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.
肿瘤靶向卟啉粒子 HerGa 对体内肿瘤具有优先毒性，并可通过荧光进行跟踪，从而实现同时检测、成像和治疗。我们最近发现了 HerGa 的另一个特性，即其细胞毒性可通过光照增强。在本研究中，我们使用荧光光学成像阐明了 HerGa 光激发介导的细胞损伤的细胞机制。具体而言，我们发现 HerGa 的光照会产生单线态氧，导致线粒体损伤和细胞色素 c 释放，从而促进细胞凋亡。了解 HerGa 诱导细胞死亡的机制，特别是在光照介导的激发条件下，可能会指导未来进一步定制这种纳米颗粒以用于其他治疗应用和提高效力的努力。
