Indomethacin-based near-infrared photosensitizer for targeted photodynamic cancer therapy.

Siriwalee Siriwibool, Sirilak Wangngae, Kantapat Chansaenpak, Sirawit Wet-Osot, Rung-Yi Lai, Parinya Noisa, Mongkol Sukwattanasinitt, Anyanee Kamkaew

Bioorganic chemistry 2022 May

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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. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Siriwalee Siriwibool, Sirilak Wangngae, Kantapat Chansaenpak, Sirawit Wet-Osot, Rung-Yi Lai, Parinya Noisa, Mongkol Sukwattanasinitt, Anyanee Kamkaew. Indomethacin-based near-infrared photosensitizer for targeted photodynamic cancer therapy. Bioorganic chemistry. 2022 May;122:105758