The Longer, the Stronger: Alkyl Chain Engineering for High-Brightness NIR-II AIE Nanoprobes towards High-Resolution In Vivo Bioimaging

Fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) has emerged as a powerful tool for in vivo bioimaging, offering deep-tissue penetration alongside superior spatiotemporal resolution and contrast. The development of high-performance probes is essential for achieving high-quality imaging outcomes. Owing to their unique photophysical properties, aggregation-induced emission (AIE) luminogens have been recognized as an ideal platform for constructing advanced NIR-II organic fluorescent probes. However, the brightness of current NIR-II AIE probes remains suboptimal concerning practical applications due to intrinsic molecular constraints and environmental quenching effects. To address 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). Notably, the optimized TT12,8-B NPs exhibit nearly fourfold higher brightness than TPE-BBT NPs, which is one of the highest-QY NIR-II AIE probes reported currently. Coupled with optimal particle size, good water dispersibility, outstanding photostability and biosafety, TT12,8-B NPs enabled high-clarity multiscale vasculature imaging in mice and rabbits, attaining an unprecedented signal-to-background ratio exceeding 10 and a record-high vascular resolution of 49 μm in diameter, setting new benchmarks in NIR-II fluorescence angiography. Furthermore, the exceptional angiographic performance of TT12,8-B NPs further facilitated early malignant tumor detection and discrimination between nascent and established tumors. This work not only introduces an excellent NIR-II fluorescent probe but also establishes an innovative molecular design paradigm to guide the development of brighter NIR-II organic emitters.