Minimally Invasive Surgical Technologies Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard D6061, Los Angeles, California 90048, USA.
J Biomed Opt. 2012 Jan;17(1):015003. doi: 10.1117/1.JBO.17.1.015003.
We recently reported that a targeted, brightly fluorescent gallium corrole (HerGa) is highly effective for breast tumor detection and treatment. Unlike structurally similar porphryins, HerGa exhibits tumor-targeted toxicity without the need for photoexcitation. We have now examined whether photoexcitation further modulates HerGa toxicity, using multimode optical imaging of live cells, including two-photon excited fluorescence, differential interference contrast (DIC), spectral, and lifetime imaging. Using two-photon excited fluorescence imaging, we observed that light at specific wavelengths augments the HerGa-mediated mitochondrial membrane potential disruption of breast cancer cells in situ. In addition, DIC, spectral, and fluorescence lifetime imaging enabled us to both validate cell damage by HerGa photoexcitation and investigate HerGa internalization, thus allowing optimization of light dose and timing. Our demonstration of HerGa phototoxicity opens the way for development of new methods of cancer intervention using tumor-targeted corroles.
我们最近报道称，一种靶向、高亮度荧光镓卟啉（HerGa）在乳腺癌的检测和治疗方面非常有效。与结构相似的卟啉不同，HerGa 具有肿瘤靶向毒性，而无需光激发。我们现在已经通过对活细胞的多模式光学成像，包括双光子激发荧光、微分干涉对比（DIC）、光谱和寿命成像，来研究光激发是否进一步调节 HerGa 的毒性。通过双光子激发荧光成像，我们观察到特定波长的光增强了 HerGa 介导的原位乳腺癌细胞线粒体膜电位的破坏。此外，DIC、光谱和荧光寿命成像使我们能够验证 HerGa 光激发引起的细胞损伤，并研究 HerGa 的内化，从而优化光剂量和时间。我们对 HerGa 光毒性的研究为使用肿瘤靶向卟啉开发新的癌症干预方法开辟了道路。
