Benzo[a]phenoselenazine-based NIR photodynamic therapy for the treatment of COX-2 overexpressing cancer cells

Upregulation of Cyclooxygenase-2 (COX-2) in a variety of cancer cell lines, a key enzyme of prostaglandin biosynthesis, relative to surrounding normal tissues results in the use of the COX-2 protein as an attractive molecular target for many anticancer therapeutics. This could have a significant implication for selective destruction of cancer cells via the photodynamic therapy effects, leaving the normal tissue intact. Here, a COX-2-specific NIR photosensitizer (Se-C₆-IMC) was synthesized and developed by conjugating a classic anti-inflammatory drug indomethacin (IMC) as an efficient recognition group for COX-2 protein, with benzo[a]phenoselenazine derivative photosensitizer through hexanediamine linker. In this study, Se-C₆-IMC exhibited a strong NIR absorption in the phototherapeutic window, relatively high ¹O₂ generation (Φ_Δ = 0.74 in CH₂C₂), and an excellent phototoxicity (IC₅₀ = 0.04 µM, 14.4 J/cm²) against MCF-7 cells as compared to COS-7 cells lacking COX-2 protein expression. Se-C₆-IMC showed the highest intracellular localization in Golgi apparatus, making it to more effective for cellular destruction and Golgi targeted therapy. Thus, Se-C₆-IMC might hold great promise as a COX-2-specific NIR photosensitizer for improving the PDT efficiency and new Golgi-targeted PDT development in the future.