AbstractAggregation-induced emission nanoparticles serve as promising fluorescence probes for multi-photon excitation microscopy due to the large absorption cross-section at NIR-IIb region. Here we present organic AIE nanoparticles that feature high aborption cross-section under three-photon excitation. We show that these enable ultra-deep NIR-IIa excited three-photon imaging in the in-vivo mouse brain.