Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters(Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin(BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid(FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ∼5.7% at pH 7.4 in phosphate buffer saline(PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy(XPS) suggests binding energies correlating to metal Au4f7/2∼83.97eV and Au4f5/2∼87.768eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ∼1nm and protein cluster aggregates of size ∼8nm. Photoluminescence studies show bright fluorescence with peak maximum at ∼674nm with the spectral profile covering the near-infrared(NIR) region, making it possible to image clusters at the 700-800nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500νgml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer. © IOP Publishing Ltd.
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A. Retnakumari, Setua, S., Menon, D., Ravindran, P., Muhammed, H., Pradeep, T., Nair, S., and Koyakutty, M., “Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging”, Nanotechnology, vol. 21, 2010.