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

The development of bright and stable 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 AIE‑active NIR‑II dye TPE‑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 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.