Alkyl Chain Engineering for High-Brightness Near-Infrared-II Aggregation-Induced Emission Nanoprobes toward High-Resolution <i>In Vivo</i> Bioimaging

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) has emerged as a powerful tool for <i>in vivo</i> bioimaging, offering deep-tissue penetration alongside high spatiotemporal resolution and contrast. Owing to structural advantages, aggregation-induced emission (AIE) luminogens are recognized as an ideal platform for constructing advanced NIR-II organic probes. However, their brightness remains suboptimal for practical applications due to intrinsic molecular constraints and environmental quenching effects. Addressing these issues, a high-brightness NIR-II AIE nanoprobe, TT12,8-B NPs, was developed based on the proposed design strategy of increasing molecular alkyl lengths, which simultaneously enhances aggregate hydrophobicity and expands intermolecular packing distance, synergistically improving both molar absorptivity and quantum yield (QY). The optimized TT12,8-B NPs exhibit nearly 4-fold higher brightness than TPE-BBT NPs, one of the highest-QY NIR-II AIE probes reported. Coupled with good photostability and biocompatibility, TT12,8-B NPs enabled high-clarity multiscale vasculature imaging in mice and rabbits, attaining a high signal-to-background ratio exceeding 10 and a tiny vascular resolution of 49 μm in diameter, moving forward in NIR-II fluorescence angiography. Their exceptional angiographic performance further facilitated early tumor detection and discrimination between nascent and established tumors. Beyond the introduction of an excellent NIR-II fluorophore, this work provides an advanced molecular design philosophy.