Constitutional Isomerization Enables Bright NIR‐II AIEgen for Brain‐Inflammation Imaging

Abstract The shortage of high quantum yield (QY) organic fluorophores in the second near‐infrared window (NIR‐II) has become a bottleneck in bioimaging field. Now, a simple strategy is proposed to address this: constitutional isomerization on the basis of the molecular design philosophy of aggregation‐induced emission. With the combination of backbone distortion and rotor twisting, the resultant NIR‐II fluorophore 2TT‐ o C6B displays an emission peak at 1030 nm and a QY of 11% in nanoparticles, one of the highest reported so far. Control molecules confirm that the distorted backbone and twisted rotors play equally important roles in determining the fluorescence properties of the NIR‐II fluorophores. To allow for the targeting ability to reach deeply located diseases, neutrophils (NEs) are used to penetrate the brain tissues and accumulate in the inflammation site. Herein, it is shown that NEs carrying 2TT‐ o C6B nanoparticles can penetrate the blood‐brain‐barrier and visualize the deeply located inflammation through an intact scalp and skull. Notably, the bright 2TT‐ o C6B contributes to a significantly enhanced signal‐to‐background ratio of 30.6 in the brain inflammation site.