Aza-BODIPY dye with unexpected bromination and high singlet oxygen quantum yield for photoacoustic imaging-guided synergetic photodynamic/photothermal therapy

Introducing heavy halogen atoms into organic small molecules is a practical strategy for efficient singlet oxygen (¹O₂) generation. Generally, bromine or iodine atoms are introduced on the aza-boron-dipyrromethene (aza-BODIPY) core, rather than on the periphery aryl rings for efficient ¹O₂ generation. Herein, an aza-BODIPY dye NBDPBr with unexpected bromination on the periphery aryl rings was synthesized for photoacoustic (PA) imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) in tumor cells. Owing to unexcepted bromination at the periphery aryl rings, NBDPBr demonstrated an outstanding singlet oxygen quantum yield (Φ_Δ) of 66% which was superior to similar brominated photosensitizers previously reported. After encapsulation with amphiphilic polymer F-127, hydrophilic NBDPBr nanoparticles (NPs) were fabricated and exhibited an excellent photothermal conversion efficiency (η) of 43.0% under 660 nm photoirradiation. In vivo PA imaging results demonstrated that NBDPBr NPs could specifically accumulate at tumor sites and realized the maximum tumor retention at 7 h post-injection. All the in vitro and in vivo results indicated the significant potence of NBDPBr with unexpected bis-bromination for PA imaging-guided synergetic PDT/PTT.