n-Hexyl Side Chain Engineering: Crafting NIR-II AIEgens with Balanced Fluorescence-Photothermal Performance for Precision Tumor Ablation

Photothermal therapy (PTT) has gained significant attention as a promising cancer treatment due to its low systemic toxicity, minimal invasiveness, and other advantages. Aggregation-induced emission luminogens (AIEgens) with second near-infrared (NIR-II) fluorescence have emerged as ideal photothermal agents (PTAs), offering key benefits such as high biosafety, excellent biocompatibility, and precise tumor theranostics. Nevertheless, achieving an optimal balance between radiation-mediated NIR-II fluorescence imaging and non-radiation NIR-PTT poses a considerable challenge in designing efficient NIR-II AIEgens. In this work, we employed side chain engineering by strategically grafting n -hexyl onto the π-bridge of a conjugated D-π-A-π-D structure, leading to the development of four new AIEgens ( BQ1 ∼ BQ4 ). These compounds feature 6,7-diphenyl- [1,2,5] thiadiazolo [3,4- g ] quinoxaline as the acceptor, thiophene as the π-bridge, and phenothiazine as the donor. This molecular design enables precise regulation of backbone distortion, effectively balancing fluorescence emission and photothermal conversion. Among them, BQ1 , BQ3 , and BQ4 exhibited strong fluorescence, longer emission wavelengths, and superior photothermal conversion efficiencies (PCEs) (59.2%, 57.8%, 52% respectively), whereas BQ2 , with greater molecular distortion, showed a lower PCE of 33.4%. Notably, BQ1 nanoparticles demonstrated outstanding photothermal conversion, prolonged tumor retention, strong resistance to photobleaching in vitro and in vivo , and NIR-II imaging capability at 1055 nm. This study introduces a novel strategy for optimizing NIR-II/AIE PTAs through precise conformational control via strategic n -hexyl positioning, which remains unreported to date.