Abstract
BACKGROUND: Construction of nanoprobes for dual-modal fluorescence/photoacoustic imaging (PAI) is of great importance for the detection of disease pathology and the development of innovative therapeutics. Previously ultra-small gold clusters were designed and used as contrast agents for fluorescence imaging (FLI). However, it is not clear whether they can also serve as promising probes for PAI. In this study, protein-modified ultra-small gold clusters are produced and examined quantitatively as enhanced contrast agents for dual-modal in vivo fluorescence and PAI. METHODS: To construct the dual-modal ultra-small gold clusters, HAuCl(4)·4H(2)O aqueous solution was first mixed with the protein solution. NaOH was further introduced to the solution under vigorous stirring. The as-designed dual-modal nanoprobe was formed after stirring for 2 h at 65 °C. And then the solution was purified by gel column for further application. Zebrafish, cultivated in the solution containing gold clusters, was used in this study to demonstrate the dual-modal imaging ability of the nanoprobe by using our home-made optical-resolution photoacoustic microscopy and commercial fluorescence microscopy systems. RESULTS: The gold nanoclusters were synthesized with diameters of about 3 nm, which showed the broad absorption with a characteristic peak centered at 520 nm. A strong near-infrared emission ranging from 600 to 750 nm was also observed for the gold clusters. In addition, the cell viability was more than 90% even at a high concentration of the nanoprobes. The zebrafish cultivated with the gold clusters exhibited dramatically enhanced fluorescence and photoacoustic signal intensities. CONCLUSIONS: Quantitative analysis results demonstrated that BSA-modified gold clusters were excellent contrast agents for in vivo dual-modal fluorescence/PAI. Due to their ultra-small size and superior biocompatibility, they can be applied to the detection and treatment of various diseases with enhanced sensitivity.