An aza-BODIPY photosensitizer for photoacoustic and photothermal imaging guided dual modal cancer phototherapy

Developing biocompatible, near infrared absorbing, and multi-functional photosensitizers is crucial for effective cancer phototherapy. In this contribution, a BF₂ chelate of [4-iodo-5-(4-bromophenyl)-3-(4-methoxyphenyl)-1H-pyrrol-2-yl][4-iodo-5-(4-bromophenyl)-3-(4-methoxyphenyl)pyrrol-2-ylidene]amine (IABDP) with high singlet oxygen generation efficiency (∼92%) has been designed and synthesized. Soluble and near infrared absorbing nanoparticles (NPs) can be simply obtained from the self-assembly of IABDP molecules, which have a high photothermal conversion efficiency (∼37.9%). Under irradiation of a broadband Xenon lamp, IABBDP NPs are able to serve as common photosensitizers for photothermal imaging (PTI) and photoacoustic imaging (PAI) guided simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT). Compared to the usual combined strategies that require two distinct photosensitizers and two excitation sources, the IABBDP NP based approach is simplified considerably, and hence is more convenient, reliable, and cost effective. Both in vitro and in vivo studies confirm the good biosafety and prominent anti-tumor phototoxicity of IABDP NPs. Finally, we demonstrate that the imaging guided synergistic dual modal phototherapy enabled by IABDP NPs can essentially inhibit tumor growth (87.2% inhibition) in mice without causing considerable side-effects, testifying the great potential of this multi-functional organic photosensitizer for clinical use.