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-borondipyrromethene（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（ΦΔ） 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.