纳米金颗粒与蛋白质分子的相互作用以及其入胞机制的研究

There is currently growing interest in the clinical applications of Gold nanoparticles (AuNPs) in areas such as: drug delivery, in vivo diagnostics, genetic materials and photothermal therapy. The interaction between AuNPs and living system are commonly mediated by the formation of protein corona, which may change its specific targeting capability and cause undesirable biological effects. For application-driven surface modifications, it is essential to study the nanoparticle-protein interactions. However, the study is largely limited by the lack of quantitative measurement technique and fundamental interaction theory. To address this issue，this study will utilize surface plasmon resonance（SPR）technology to monitor the interface interactions on AuNPs. In combination of other biochemical measurements, this study will focus on the impact of particular chemical modification on cell, revealing the mechanisms for cell adhesion and cell uptake. This study will also establish a novel technological platform for nanoparticle－protein interface studies, enabling the characterization of AuNPs-protein corona complex and opens up the possibilities for rational design for AuNPs.

纳米金颗粒被广泛的应用在药物传输、体内诊断、基因调控试剂以及光反应治疗药物等临床研究。纳米金颗粒进入人体后，不可避免的会吸附体液中的蛋白质分子，在表面形成蛋白质冠，对其生物学功能产生重大影响。研究金颗粒-蛋白质的相互作用以及定向优化纳米金颗粒表面的化学修饰具有重大的意义和应用前景。目前，评估化学修饰后金颗粒与蛋白质的界面作用仍然面临着局限性，尤其是缺乏有效的量化测量方法。本研究拟在前期研究的基础上应用表面等离子共振（SPR）技术，建立一套纳米金颗粒和血清蛋白相互作用的评价方法。 SPR技术的优势在于实时并精确地测量纳米金颗粒蛋白质冠的形成过程和界面作用。本项目将通过测量不同的纳米金颗粒表面化学修饰的特性，进而观察细胞实验结果，建立构效关系，揭示其黏附细胞表面和入胞的机理，为纳米颗粒-蛋白质的界面研究提供重要的方法学，同时也为纳米金颗粒的理性设计奠定基础。