An AIE-active centrosymmetric small molecule for ultra-deep three-photon brain angiography in the NIR-III window

• • T4PQ NPs achieved a three-photon imaging depth of 1785 μm in murine cerebrovasculature, surpassing conventional probes and enabling visualization of deep brain structures critical for neurovascular studies. • • Real-time hemodynamic monitoring was performed at 1006 μm depth, demonstrating the probe's capability to capture dynamic blood flow in microvessels, essential for understanding neurovascular coupling. • • The centrosymmetric design enhanced the three-photon absorption cross-section and fluorescence quantum yield, leading to a high three-photon action cross-section (ησ3), which directly improves signal-to-noise ratio in deep-tissue imaging. • • T4PQ NPs exhibited excellent photostability and biocompatibility, addressing key limitations of quantum dots (e.g., toxicity) and ensuring suitability for long-term in vivo imaging.