Molecularly manipulating pyrazinoquinoxaline derivatives to construct NIR-II AIEgens for multimodal phototheranostics of breast cancer bone metastases.

Abstract

Multimodal phototheranostics on the basis of single molecular species shows inexhaustible and vigorous vitality, particularly those emit fluorescence in the second near-infrared window (NIR-II), the construction of such exceptional molecules nonetheless retains formidably challenging. In view of the undiversified molecular skeletons and insufficient phototheranostic outputs of previously reported NIR-II fluorophores, herein, electron acceptor engineering based on heteroatom-inserted rigid-planar pyrazinoquinoxaline was manipulated to fabricate aggregation-induced emission (AIE)-featured NIR-II counterparts with donor-acceptor-donor (D-A-D) architecture. Systematical investigations substantiated that one of those synthesized AIE molecules, namely 4TPQ, incorporating a fused thiophene acceptor, synchronously exhibited high molar absorptivity (ε), NIR-II emission, typical AIE tendency, significant reactive oxygen species (ROS) generation, and high photothermal conversion efficiency. These extraordinary behaviors endowed 4TPQ nanoparticles with unprecedented performance on NIR-II fluorescence/photothermal imaging-navigated synergistic photodynamic/photothermal inhibition of tumors, as confirmed by the mice model of breast cancer bone metastases. This study thus brings significant insights into developing phototheranostic systems for clinical trials.