Zhang Bingbo, Wang Jun, Yu Jiani, Fang Xiangming, Wang Xiuli, Shi Donglu
Institute of Photomedicine, Shanghai Skin Disease Hospital; The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine , Shanghai 200443, China.
Department of Radiology, Wuxi People's Hospital, Nanjing Medical University , Wuxi 214023, China.
Bioconjug Chem. 2017 Feb 15;28(2):330-335. doi: 10.1021/acs.bioconjchem.6b00712. Epub 2017 Jan 20.
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 Au ion coordination motifs and a Gd 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.
人们已经制备了各种仿生纳米颗粒，用于癌症的纳米诊疗，这些纳米颗粒结合了多种蛋白质。然而，这些反应的作用机制仍不清楚，尤其是金属离子与蛋白质之间的相互作用、精确的结合位点以及纳米颗粒的存在形式。假设将氨基酸序列缩短为几个，即短肽，那么研究仿生反应机制将会容易得多。在本研究中，设计并合成了一种具有金离子配位基序和钆离子螯合序列的模块化肽。实验发现，这种肽在顺磁性荧光金纳米团簇（pAuNCs）的位点特异性仿生合成中有效，其量子产率为6.8%，在676nm处发射深红色光，并且具有很强的弛豫率。凝胶电泳结果表明，pAuNCs中的两个成像基序相当稳定。在荷瘤小鼠体内进行的荧光磁共振双模态成像显示，pAuNCs对肿瘤有显著的增强作用。体内生物分布和毒性研究表明，pAuNCs可以在不造成损害的情况下逐渐从体内清除。本研究提出了一种模块化肽，它可以以仿生方式培育多功能纳米颗粒，并有望为研究蛋白质介导的仿生合成机制提供一种策略。
