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

doi:10.1016/j.bioorg.2022.105758

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

Bioorg Chem. 2022 May:122:105758. doi: 10.1016/j.bioorg.2022.105758. Epub 2022 Mar 24.

Authors

Siriwalee Siriwibool¹, Sirilak Wangngae¹, Kantapat Chansaenpak², Sirawit Wet-Osot³, Rung-Yi Lai¹, Parinya Noisa⁴, Mongkol Sukwattanasinitt⁵, Anyanee Kamkaew⁶

Affiliations

¹ School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
² National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand.
³ Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand.
⁴ Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
⁵ Thailand Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
⁶ School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand. Electronic address: anyanee@g.sut.ac.th.

PMID: 35344895
DOI: 10.1016/j.bioorg.2022.105758

Abstract

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.

Keywords: COX-2; Cancer targeting; Cy820; Heptamethine cyanine; NIR photosensitizer; Photodynamic therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Indomethacin / pharmacology
Neoplasms* / drug therapy
Photochemotherapy* / methods
Photosensitizing Agents / chemistry
Photosensitizing Agents / pharmacology

Substances

Photosensitizing Agents
Indomethacin