Bisbenzoselenophene[ b ]-Fused AzaBODIPYs as Strong Near-Infrared-Absorbing Photosensitizers for Effective Photodynamic Tumor Therapy

Abstract Photodynamic therapy (PDT) is a promising precision treatment for cancer, yet its clinical translation is often hindered by the lack of near-infrared (NIR) photosensitizers that simultaneously offer efficient reactive oxygen species (ROS) generation capability, deep-tissue penetration, and favorable biocompatibility. Herein, we report two novel bisbenzoselenophene[b]-fused azaBODIPY derivatives, Se-BDP 1 and Se-BDP 2, via a one-pot CuI-catalyzed cyclization/BF2-complexation strategy. They display strong NIR absorption (λmax up to 726 nm) and achieve ROS generation quantum yields reaching 0.27. When formulated into nanoparticles, Se-BDP 1 demonstrates exceptional biocompatibility with minimal dark toxicity, along with potent photocytotoxicity against 4T1, B16, and HeLa cells, effectively suppressing tumor cell proliferation. In vivo studies in 4T1-tumor-bearing mice reveal a high tumor-growth inhibition rate (tumor growth inhibition = 73%) without apparent systemic toxicity. Given their strong NIR absorption, efficient Type I/II ROS generation, and minimal dark toxicity, these selenium-incorporated azaBODIPYs represent a promising class of photosensitizers for clinically translatable PDT.