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 1O2 generation efficiency,
and an improved photo-dark toxicity ratio. Aspartic acid-modified
PS of 1a, which possessed intense NIR absorption and
high 1O2 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 1a were studied. In
vivo fluorescence imaging and ex vivo organ
distribution assays manifested that 1a possessed reasonable
distribution and clearance. In vivo PDT studies indicated
that 1a revealed advantages over Ce6 and
our previously optimized PS of BDP-4. 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.