Site-Specific Biomimetic Precision Chemistry of Bimodal Contrast Agent with Modular Peptides for Tumor-Targeted Imaging.

Abstract

Various biomimetic nanoparticles have been fabricated for cancer nanotheranostics with a diverse range of proteins. However, the operating mechanisms of these reactions are still unclear, especially on the interaction between metal ions and protein, the precise binding sites, and the existence format of nanoparticles. Assuming the shortening of the amino acids sequence into several, namely short peptides, it would be much easier to investigate the biomimetic reaction mechanism. In this study, a modular peptide, possessing Au3+ ion coordination motifs and a Gd3+ ion chelation sequence, is designed and synthesized. This peptide is experimentally found effective in site-specific biomimetic synthesis of paramagnetic fluorescent gold nanoclusters (pAuNCs) with a quantum yield of 6.8%, deep red emission at 676 nm, and potent relaxivity. The gel electrophoresis result declares that the two imaging motifs in pAuNCs are quite stable. In vivo fluorescence-magnetic resonance bimodal imaging show significant tumor enhancement by pAuNCs in tumor-bearing mice. In vivo biodistribution and toxicity studies reveal that pAuNCs can be gradually cleared from the body without damage. This study presents a modular peptide that can incubate multifunctional nanoparticles in a biomimetic fashion and hopefully provides a strategy for the investigation of the mechanism of protein-mediated biomimetic synthesis.