Luo Ting, Zhang Qinrong, Lu Qing-Bin
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Departments of Biology and Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Cancers (Basel). 2017 Jun 5;9(6):63. doi: 10.3390/cancers9060063.
Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer.
吲哚菁绿（ICG）已被报道为一种潜在的用于癌症光动力疗法（PDT）的近红外（NIR）光敏剂。然而，ICG介导的PDT的应用在本质上和生理上都受到限制。在此，我们报道了ICG-PDT与化疗药物依托泊苷（VP-16）的联合应用，旨在提高抗癌疗效，规避使用ICG的PDT的局限性，并减少VP-16的副作用。我们在基于细胞的体外对照试验中发现，这种联合应用在杀死非小细胞肺癌细胞（NSCLC，A549细胞系）方面是有效的。我们还发现，ICG-PDT与VP-16的联合在杀死非小细胞肺癌细胞方面表现出强烈的协同作用，部分是通过诱导更多的DNA双链断裂（DSB），而在杀死人类正常细胞（GM05757）方面协同作用较弱。此外，通过研究ICG和VP-16激光照射混合物的治疗顺序依赖性和细胞毒性，我们发现观察到的协同作用涉及ICG和VP-16之间的直接/间接反应。我们进一步提出，在照射下ICG和VP-16之间存在电子转移反应。因此，本研究显示了ICG-PDT与VP-16联合应用的抗癌疗效。这些发现表明，ICG介导的PDT可与化疗药物VP-16联合应用于治疗某些癌症，尤其是非小细胞肺癌。
