Highly Luminescent Folate‐Functionalized Au22 Nanoclusters for Bioimaging

Gold nanoclusters are emerging as new materials for biomedical applications because of promises offered by their ultrasmall size and excellent biocompatibility. Here, the synthesis and optical and biological characterizations of a highly luminescent folate‐functionalized Au22 cluster (Au22‐FA) are reported. The Au22‐FA clusters are synthesized by functionalizing the surface of Au22(SG)18 clusters, where SG is glutathione, with benzyl chloroformate and folate. The functionalized clusters are highly water‐soluble and exhibit remarkably bright luminescence with a quantum yield of 42%, significantly higher than any other water‐soluble gold clusters protected with thiolate ligands. The folate groups conjugated to the gold cluster give rise to additional luminescence enhancement by energy transfer sensitization. The brightness of Au22‐FA is found to be 4.77 mM−1 cm−1, nearly 8‐fold brighter than that of Au22(SG)18. Further biological characterizations have revealed that the Au22‐FA clusters are well‐suited for bioimaging. The Au22‐FA clusters exhibit excellent photostability and low toxicity; nearly 80% cell viability at 1000 ppm of the cluster. Additionally, the Au22‐FA clusters show target specificity to folate‐receptor positive cells. Finally, the time‐course in vivo luminescence images of intravenous‐injected mice show that the Au22‐FA clusters are renal‐clearable, leaving only 8% of them remained in the body after 24 h post‐injection. Folate‐functionalized Au22 nanoclusters show the highest luminescence quantum yield of 42% among other water‐soluble gold nanoclusters protected with thiolate ligands. The brightness is enhanced by 8‐fold via the rigidification of the surface shell and energy transfer sensitization from the photoexcited folate. The highly luminescent gold clusters with excellent biocompatibility and active targeting ability are well‐suited to targeted bioimaging.