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

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.