Breaking Performance Limits of NIR-II AIEgens for Imaging and Photothermal Therapy via Multidimensional Molecular Engineering

The second near-infrared (NIR-II) window enables deep-tissue penetration with high spatial resolution; however, simultaneously optimizing absorption/emission wavelength, quantum yield, molar extinction coefficient, and photothermal conversion efficiency remains a central challenge. Herein, we report a benzobisthiadiazole-based fluorophore featuring a D–A–D–A–D–A–D scaffold that combines a large planar conjugated core with peripheral twisted rotors forming an AIE–ACQ–AIE architecture that effectively balances these interdependent properties. Among the synthesized derivatives, MTBTMT-BBT exhibited the most balanced photophysical and photothermal properties. Nanoparticles fabricated via F127 encapsulation exhibited stable aqueous dispersibility, red-shifted absorption, and intense NIR-II fluorescence under 808, 980, and 1064 nm excitation. In vivo, MTBTMT-BBT NPs enabled high-resolution angiography with superior signal-to-noise ratio. Under laser irradiation, the NPs reached temperatures above 60 °C with a photothermal conversion efficiency of 57.9%, completely eradicating tumors while maintaining favorable biosafety and clear superiority over indocyanine green. This work establishes a multidimensional molecular engineering strategy for developing high-performance NIR-II agents and advances multifunctional platforms toward precise cancer theranostics.