Hj‐aggregates of quinoline‐fused boron‐dipyrromethene nanoparticles for near‐infrared dualmodal photodynamic and photothermal therapy

Abstract

Abstract Development of boron‐dipyrromethene (BODIPY)‐based phototherapeutic agents integrating photodynamic and photothermal therapy is limited by restricted modifiable sites on traditional scaffolds. Herein, we report a quinoline‐fused cyclic pyrrole Npy generated by an lithium diisopropylamide‐catalyzed [3 + 2] cyclization, which incorporates a nitrogen atom into a rigid polycyclic π‐system. Using this pyrrole Npy, a symmetric photosensitizer Npy‐BDP with absorption at 660 nm was prepared with a singlet oxygen quantum yield of 0.38, and efficient type‐I reactive oxygen species generation. Upon nanoparticle encapsulation, Npy‐BDP forms Hj‐aggregates with absorption peaks at 562 and 703 nm. Npy‐BDP NPs achieve a photothermal conversion efficiency of 53% and generate local hyperthermia under 690 nm laser irradiation. In vitro Npy‐BDP NPs exhibit potent photocytotoxicity against HeLa cells with low dark toxicity and induce apoptosis through the mitochondrial pathway. In vivo intratumoral injection of Npy‐BDP NPs followed by laser irradiation resulted in sustained tumor regression. This work presents the first example of Hj‐aggregates in the BODIPY system, providing a new molecular design paradigm for phototherapy reagents.