School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand.
Bioorg Chem. 2022 May;122:105758. doi: 10.1016/j.bioorg.2022.105758. Epub 2022 Mar 24.
Near-IR fluorescent sensitizers based on heptamethine cyanine (Cy820 and Cy820-IMC) were synthesized and their abilities to target and abolish tumor cells via photodynamic therapy (PDT) were explored. Some hepthamethine cyanine dyes can be transported into cancer cells via the organic anion transporting polypeptides (OATPs). In this study, we aimed to enhance the target ability of the sensitizer by conjugation Cy820 with indomethacin, a non-steroidal anti-inflammatory drug (NSAID), to obtain Cy820-IMC that aimed to target cyclooxygenase-2 (COX-2) which overexpresses in cancer cells. The results showed that Cy820-IMC internalized the cancer cells faster than Cy820 which was verified to be related to COX-2 level and OATPs. Based on PDT experiments, Cy820-IMC has higher photocytotoxicity index than Cy820, >7.13 and 4.90, respectively, implying that Cy820-IMC showed better PDT property than Cy820. However, Cy820 exhibits slightly higher normal-to-cancer cell toxicity ratio than Cy820-IMC, 6.58 and 3.63, respectively. Overall, Cy820-IMC has superior cancer targetability and enhanced photocytoxicity. These characteristics can be further improved towards clinically approved sensitizers for PDT.
基于七甲川菁染料（Cy820 和 Cy820-IMC）的近红外荧光敏化剂被合成，并探索了它们通过光动力疗法（PDT）靶向和消灭肿瘤细胞的能力。一些七甲川菁染料可以通过有机阴离子转运多肽（OATPs）被转运到癌细胞中。在这项研究中，我们旨在通过将 Cy820 与非甾体抗炎药（NSAID）吲哚美辛偶联，来增强敏化剂的靶向能力，获得旨在靶向在癌细胞中过表达的环氧化酶-2（COX-2）的 Cy820-IMC。结果表明，Cy820-IMC 比 Cy820 更快地内化癌细胞，这被证实与 COX-2 水平和 OATPs 有关。基于 PDT 实验，Cy820-IMC 的光细胞毒性指数高于 Cy820，分别为>7.13 和 4.90，这意味着 Cy820-IMC 比 Cy820 具有更好的 PDT 性能。然而，Cy820 比 Cy820-IMC 表现出略高的正常细胞对癌细胞毒性比，分别为 6.58 和 3.63。总的来说，Cy820-IMC 具有优越的癌症靶向性和增强的光细胞毒性。这些特性可以进一步改进为临床批准的 PDT 敏化剂。
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