Ultrasmall Red Fluorescent Gold Nanoclusters for Highly Biocompatible and Long‐Time Nerve Imaging

A rapidly growing area of neuroscience demands next-generation neurofluorescent probes are fulfilling several stringent criteria, including water solubility, distinct signal-to-background ratio, anti-photobleaching, and low toxicity. Herein, a novel neurofluorescent probe based on gold nanoclusters capped with glutathione (Au-GSH) is introduced and characterized by advanced fluorescence photophysical properties composed of comparative high quantum yield (8.9%), negligible blinking, and bright fluorescence in the red spectral range (E-m = 650 nm) with sub-millisecond-scale lifetime (0.62 ms). Fluorescent performance is tested and demonstrated negligible photobleaching under exposure to ultraviolet light (365 nm, 30 W) over 4 h, immunity to variation of the microenvironment characterized by pH range of 4-10, and colloidal stability in serum over 24 h during the blood circulation. Coupled with 2.4 +/- 0.9 nm ultrasmall size and good water solubility, they are superior to fluorescent proteins, quantum dots, and organic fluorescent dyes. Au-GSH are further confirmed that they can be used as a fluorescent label for in vivo nerve and brain imaging, and even after injecting Au-GSH into the rat sciatic nerve for 21 d, the red fluorescence is still preserved. This combination of favorable properties makes Au-GSH a promising candidate for neurofluorescent probes.