Discovery of an Amino Acid-Modified Near-Infrared Aza-BODIPY Photosensitizer as an Immune Initiator for Potent Photodynamic Therapy in Melanoma.

The discovery of novel photosensitizers with potent phototoxicity and desirable water solubility is an urgent task for photodynamic therapy. Herein, a series of amino acid-modified aza-BODIPY photosensitizers were synthesized and evaluated. These new PSs exhibited enhanced aqueous solubility, increased O generation efficiency, and an improved photo-dark toxicity ratio. Aspartic acid-modified PS of , which possessed intense NIR absorption and high O quantum yield, demonstrated the most potent efficacy toward the investigated tumor cell lines without using an emulsifier. Subcellular localization, cell-based ROS production, and cell death pathway of were studied. fluorescence imaging and organ distribution assays manifested that possessed reasonable distribution and clearance. PDT studies indicated that revealed advantages over and our previously optimized PS of . It not only afforded an excellent PDT effect with a low drug dose under only single-time photoirradiation but also induced an antitumor immunological response.