A water-soluble and near-infrared indomethacin-modified BODIPY photosensitizer for tumor-targeting photodynamic therapy

Abstract

Enhancement of spatial precision in photodynamic therapy (PDT) is critical for effective tumor eradication. For achieving this requirement, the development of structurally tailored photosensitizers with high tumor specificity and retention in vivo, is still a significant challenge. Herein, a novel, water-soluble near-infrared (NIR) BODIPY-based photosensitizer integrated with indomethacin (I-M-BDP), featuring a targeted characteristic toward cyclooxygenase-2 (COX-2, a well-recognized oncogenic enzyme overexpressed in various tumors), was designed and synthesized successfully. In this targeted BODIPY photosensitizer, the COX-2 targeting moiety is precisely incorporated into the molecular architecture to confer selective tumor accumulation. The I-M-BDP exhibits excellent imaging performances, perfect biocompatibility, high photostability, and efficient singlet oxygen generation under NIR irradiation. In vivo imaging and therapeutic studies utilizing a Balb/c tumor-bearing mouse model reveal that I-M-BDP preferentially localizes within tumor tissues exhibiting elevated COX-2 expression, resulting in significant tumor accumulation. Correspondingly, I-M-BDP demonstrated remarkable PDT efficacy, achieving up to 96% tumor growth inhibition upon 660 nm laser irradiation, with minimal off-target effects. This COX-2-targeting photosensitizer exhibits promising potential for minimally invasive, highly selective tumor treatment, paving the way for advanced personalized PDT strategies. Graphical abstract: [Figure not available: see fulltext.]