Site-Specific Biomimetic Precision Chemistry of Bimodal Contrast Agent with Modular Peptides for Tumor-Targeted Imaging
Site-Specific Biomimetic Precision Chemistry of Bimodal Contrast Agent with Modular Peptides for Tumor-Targeted Imaging
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用于肿瘤靶向成像的双峰造影剂与模块化肽的位点特异性仿生精密化学
DOI：
10.1021/acs.bioconjchem.6b00712
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发表时间：
2017
影响因子：
4.7
通讯作者：
Shi Donglu
中科院分区：
文献类型：
--
作者：
Zhang Bingbo;Wang Jun;Yu Jiani;Fang Xiangming;Wang Xiuli;Shi Donglu
各种仿生纳米颗粒已被制造用于癌症纳米治疗诊断与各种蛋白质。然而，这些反应的运行机制仍然不清楚，特别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，这将更容易研究仿生反应机理。在这项研究中，一个模块肽，具有Au 3+离子配位基序和Gd 3+离子螯合序列，设计和合成。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是有效的，量子产率为6.8%，在676 nm处发射深红色，并且具有有效的弛豫性。凝胶电泳结果表明，pAuNCs中的两个成像基序是相当稳定的。体内荧光-磁共振双峰成像显示，在荷瘤小鼠中，pAuNCs显著增强肿瘤。体内生物分布和毒性研究表明，pAuNCs可以逐渐从体内清除而不会造成损伤。本研究提出了一个模块化的肽，可以孵育多功能纳米粒子在仿生的方式，并希望提供一个策略，研究蛋白质介导的仿生合成的机制。
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.