Photodynamic therapy based on indomethacin-conjugated photosensitizers: targeting cyclooxygenase-2 in cancer treatment

Photodynamic therapy is a non-invasive treatment that directly kill cancer cells through the generation of reactive oxygen species. However, photodynamic therapy can also paradoxically trigger harmful protumorigenic effects, such as overexpression cyclooxygenase-2 and secretion of prostaglandin E2 in various type of tumors, limiting the overall therapeutic efficacy of photodynamic therapy. The inhibition of prostaglandin E2 secretion using nonselective cyclooxygenase inhibitors such as indomethacin, a widely used anti-inflammatory drug, with photodynamic therapy offers a promising approach for reducing light-induced inflammation and enhancing the effectiveness of photodynamic therapy. In addition, indomethacin and other cyclooxygenase-2 inhibitors have been conjugated with other therapeutic agents to develop tumor-targeted drug delivery systems. Their ability to selectively target and accumulate in cancer cells makes them attractive for delivering a wide range of photosensitizers directly to diseased tissues. Given the considerable progress in this area, this review outlines the photodynamic therapy application of various indomethacin-conjugated photosensitizers for the treatment of cyclooxygenase-2 overexpressed tumor cells, aiming to improve light-mediated effectiveness and reduce off-target effects. Finally, we highlight and discuss future perspectives and challenges in the development of indomethacin-conjugated photodynamic therapy agents.