Synthesis and Photodynamic Activities of Pyridine- or Pyridinium-Substituted Aza-BODIPY Photosensitizers.

In this work, various novel pyridinyl- and pyridinium-modified Aza-BODIPY PSs were designed and constructed based on monoiodo Aza-BODIPY PSs ( and ) in an attempt to construct "structure-inherent organelles-targeted" PSs to endow potential organelle-targeting ability. Pyridinyl PSs displayed potent photodynamic efficacy, and monorigidified PSs were very effective. The monorigidified PS with -pyridinyl moiety displayed the most potent photoactivity and negligible dark toxicity with a favorable dark/phototoxicity ratio (>4800). To our surprise, monorigidified PS with -pyridinyl moiety (e.g., ) was lipid droplet-targeted. showed good cellular uptake and intracellular ROS generation compared with . The preliminary cell death process exploration indicated that resulted in lipid peroxidation and induced cell death through an iron-independent ferroptosis-like cell death pathway. In vivo antitumor efficacy experiments manifested that significantly inhibited tumor growth and outperformed and even under a single low-dose light irradiation (30 J/cm).