Ultrastable TPE-DNA nanoaggregates enable bright NIR-II fluorescence vascular imaging

The development of bright and stable near-infrared II (NIR-II) fluorescent probes is crucial for deep-tissue vascular imaging but remains challenging due to dye leakage and poor carrier stability. Here, we report a multivalent tetraphenylethylene (TPE) modification strategy to construct DNA amphiphiles that self-assemble into ultrastable nanoaggregates. Unlike conventional C18-DNA or cholesterol-DNA assemblies that readily dissociate, our 7-TPE-DNA nanoaggregates remain intact even under denaturing conditions, owing to cooperative π-π stacking among multiple TPE units. The same hydrophobic core efficiently loads the aggregation-induced emission (AIE)-active NIR-II dye TPE-benzobisthiadiazole (BBT), affording bright nanoprobes with outstanding resistance to dye leakage. Following intravenous injection into living mice, the probe enables high-resolution visualization of femoral arteries and subcutaneous capillary networks with markedly improved signal-to-background ratios compared to polyethylene glycol (PEG)- or F127-based controls. This work establishes a multivalent AIE engineering strategy for DNA amphiphiles, providing a robust and versatile nanoplatform for advanced NIR-II bioimaging applications.