Bright AIEgen-Protein Hybrid Nanocomposite for Deep and High-Resolution In Vivo Two-Photon Brain Imaging

Abstract

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Two-photon fluorescence imaging allows in vivo study of biological structures and activities in deep tissues, in which bright fluorophores with high photostability and good biocompatibility are highly desirable. Herein, a small-molecule fluorogen with aggregation-induced emission (AIEgen) is complexed with fetal bovine serum (FBS) proteins to develop a protein-sized AIEgen–protein hybrid nanocomposite (TPEPy-FBS) with bright far-red/near-infrared (NIR) emission, excellent photostability, and low phototoxicity for deep and high-resolution in vivo two-photon brain vasculature imaging. Upon complexation with FBS, the fluorescence of TPEPy is greatly intensified and a sixfold enhancement is observed with 10% FBS in aqueous media. The yielded TPEPy-FBS shows good physical stability in aqueous media and the phototoxicity of TPEPy is dramatically inhibited after complexation with FBS. Moreover, TPEPy-FBS exhibits bright two-photon fluorescence in far-red/NIR region and good photostability upon femtosecond laser excitation, which facilitates high performance in vivo imaging. A large imaging depth of 656 µm is obtained in brain vasculature network imaging with a high signal-to-background ratio of 234, where a small blood capillary of 1.05 µm can be resolved at an imaging depth of 656 µm. Highlighted is a simple and versatile strategy to develop efficient two-photon probes for in vivo biological imaging.