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

Sep 23, 2026

Uploaded by kopisore

Photodynamic therapy is a non-invasive cancer treatment that directly kills cancer cells by generating reactive oxygen species, yet it can paradoxically induce harmful protumorigenic inflammation. Cyclooxygenase-2 overexpression and prostaglandin E2 secretion in many tumors restrict overall PDT efficacy. Using the cyclooxygenase inhibitor indomethacin to inhibit prostaglandin E2 release during PDT reduces light-induced inflammation and improves therapeutic effectiveness. Indomethacin-conjugated photosensitizers further enable targeted delivery and improved tumor accumulation. This review summarizes indomethacin-conjugated photosensitizers targeting COX-2-positive tumors and highlights future perspectives and development challenges.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Search Strategy

Photodynamic Therapy and Its Mechanism

Indomethacin-Conjugated Photosensitizers

Discussion

Conclusion and Outlook

Contents lists available at Wolters Kluwer-Medknow Medical Gas Research journal [homepage: www.medgasres.com](homepage: www.medgasres.com) Photodynamic therapy based on indomethacinconjugated photosensitizers: targeting cyclooxygenase-2 in cancer treatment Kalayou Hiluf Gebremedhin1, *, Birhanu Kahsay Meresa2 [https://doi.org/10.4103/mgr.MEDGASRES-D-25-00210](https://doi.org/10.4103/mgr.MEDGASRES-D-25-00210) | Date of submission: July 16, 2025 | | --- | | Date of decision: August 26, 2025 | | Date of acceptance: October 26, 2025 | Date of web publication: March 11, 2026 From the Contents | Introduction | | --- | | Search Strategy | | Photodynamic Therapy and Its Mechanism | | Indomethacin-Conjugated Photosensitizers | | Discussion | | Conclusion and Outlook | Facts 1. Photodynamic therapy (PDT) kills cancer cells via the generation of reactive oxygen species but can also trigger harmful protumorigenic effects. 2. Cyclooxygenase-2 (COX-2) overexpression and prostaglandin E2 secretion limit PDT efficacy in many tumors. 3. Combining indomethacin (IMC) COX-2 inhibitor with photosensitizer reduces inflammation and enhances PDT treatment. 4. IMC-conjugated photosensitizers show promising targeted, improved tumor accumulation, and effective cancer phototherapy. Open Questions 1. How can PDT-induced protumorigenic inflammation be effectively minimized? 2. Can IMC conjugation with photosensitizers inhibit inflammation and improve the accumulation of photosensitizers in cancer cells? 3. What design strategies best optimize IMC-conjugated photosensitizers? Abstract 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. Key Words: cancer treatment; cell death; conjugate; cyclooxygenase-2; indomethacin; near infrared; photodynamic therapy; photosensitizer; phototherapy; reactive oxygen species | Introduction
CCancer is the most frequently diagnosed disease. In 2022, there were about 20 million new cases, 9.7 million deaths, and 53.7 million 5-year prevalent cases . 1,2 This growing burden underscores the urgent need for effective, targeted, and minimally invasive therapies . Among them, photodynamic therapy (PDT) has gained significant attention asa promising alternative and clinically approved | cancer treatment .3 The overall therapeutic outcomes of PDT depend on three key elements: a photosensitizer (PS; drug or dye), molecular oxygen, and light of a specific wavelength. PDT uses non-toxic PSs that are pharmaco logically active only after exposure to a specific wavelength of light in the presence of molecu

FAQs

Why can photodynamic therapy lead to protumorigenic effects?

PDT generates reactive oxygen species that kill cancer cells, but it can also trigger harmful protumorigenic inflammation. In many tumors, PDT is limited by cyclooxygenase-2 overexpression and prostaglandin E2 secretion.

How does indomethacin improve photodynamic therapy outcomes?

Indomethacin inhibits cyclooxygenase activity, reducing prostaglandin E2 secretion during PDT. This helps minimize light-induced inflammation and enhances PDT effectiveness.

What advantage do indomethacin-conjugated photosensitizers provide?

Indomethacin-conjugated photosensitizers can selectively target and accumulate in cancer cells. This improves tumor delivery of photosensitizers and supports effective light-mediated cancer phototherapy.

Sep 23, 2026

Uploaded by kopisore