Bright Aggregation-Induced-Emission Dots for Targeted Synergetic NIR-II Fluorescence and NIR-I Photoacoustic Imaging of Orthotopic Brain Tumors

Precise diagnostics are of significant importance to the optimal treatment outcomes of patients bearing brain tumors. NIR-II fluorescence imaging holds great promise for brain-tumor diagnostics with deep penetration and high sensitivity. This requires the development of organic NIR-II fluorescent agents with high quantum yield (QY), which is difficult to achieve. Herein, the design and synthesis of a new NIR-II fluorescent molecule with aggregation-induced-emission (AIE) characteristics is reported for orthotopic brain-tumor imaging. Encapsulation of the molecule in a polymer matrix yields AIE dots showing a very high QY of 6.2% with a large absorptivity of 10.2 L g⁻¹ cm⁻¹ at 740 nm and an emission maximum near 1000 nm. Further decoration of the AIE dots with c-RGD yields targeted AIE dots, which afford specific and selective tumor uptake, with a high signal/background ratio of 4.4 and resolution up to 38 µm. The large NIR absorptivity of the AIE dots facilitates NIR-I photoacoustic imaging with intrinsically deeper penetration than NIR-II fluorescence imaging and, more importantly, precise tumor-depth detection through intact scalp and skull. This research demonstrates the promise of NIR-II AIE molecules and their dots in dual NIR-II fluorescence and NIR-I photoacoustic imaging for precise brain cancer diagnostics.