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

Abstract 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.