Stable Twisted Conformation Aza-BODIPY NIR-II Fluorescent Nanoparticles with Ultra-Large Stokes Shift for Imaging-Guided Phototherapy

Abstract

Fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) holds great promise for in vivo imaging and imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. It is very appealing to obtain NIR-II fluorescent probes through simple procedures and economical substrates. Herein, we developed a D-A-D structure NIR-II photosensitizer (Triphenylamine modified Aza-Bodipy, TAB) based on the strong electron-withdrawing nature of borane difluoride azadipyrromethene’s center(aza-BODIPY). Subsequently, halogen atoms (Br, I) are introduced to the TAB molecule, TAB-2Br and TAB-2I were synthesized. DFT calculations demonstrated the twisted conformations of the TABs, which would effectively prevent π–π stacking in the aggregate state, to restrain the aggregation-caused quenching (ACQ). Compared to the TAB molecule, significant redshifts in emission wavelength, ultra-large Stokes shift (>360 nm), and enhanced singlet oxygen production capacity were acquired for the halogenated molecules. After encapsulated by an amphiphilic polypeptide POEGMA 23-PAsp20 there formed nanoparticles via self-assembly, and the obtained P-TAB, P-TAB-2Br and P-TAB-2I nanoparticles possessed excellent water solubility and biocompatibility, remarkable photothermal conversion efficiency (beyond 40%), good resistance to photobleaching, heat, and H2O2. Under 808 nm laser irradiation, the P-TAB-2Br exhibited efficient NIR-II fluorescence emission, and the abdominal vessel of the mouse could be clearly distinguished from the surrounding background tissue. In vitro and in vivo experiments revealed that P-TABs display excellent cell lethality and tumor ablation results under 808 nm irradiation. All of these results make the TABs potential organic probes for clinical NIR-II fluorescence imaging and cancer phototherapy.