Ultrabright NIR‐II Nanoparticles for High‐Resolution In Vivo Imaging: From Systemic Vasculature Visualization to Pathological Microenvironment Monitoring

Highly emissive fluorescence probes are crucial for precise disease diagnosis. To overcome the persistent limitations of low quantum yield in near-infrared-II (NIR-II) organic dyes, an aggregation-induced emission (AIE) luminogen, TPE-Hexoxyl, has been strategically designed. By synergistically suppressing π-π stacking and minimizing intramolecular charge transfer, we engineered NIR-II nanoparticles that rank among the brightest organic probes reported (absolute Φ_PL = 0.9%). In vitro studies demonstrated that TPE-Hexoxyl nanoparticles exhibit exceptional colloidal stability and remarkable photostability. In vivo imaging displayed its high spatial resolution and prolonged tissue retention, enabling dynamic high-contrast visualization of systemic vasculature, cerebral microvasculature, and lymphatic networks. Remarkably, TPE-Hexoxyl nanoparticles show superior sensitivity in detecting tumor lesions in orthotopic 4T1 tumor-bearing mice models and achieve precise spatial mapping of inflammatory regions in inflammatory bowel disease models, underscoring their transformative potential for clinical pathological diagnostics. This work establishes a molecular modulation paradigm for designing high-brightness organic NIR-II fluorophores, providing an advanced molecular tool for further clinical diagnostic applications.