应用高通量表面等离子共振技术系统研究纳米粒子与生物分子相互作用

The molecular mechanism of the interaction between nanomaterials and biological systems is crucial for the safety assessment and biomedical applications of nanomaterials. Therefore, the study of the interaction between nanomaterials and proteins has become a hot topic. Yet, systematic study is still rare, and no general principle has been revealed; some studies even show contradictory results. Therefore, there is an urgent demand of systematic study on the interaction between nanoparticles and a large number of proteins under various conditions by high-throughput methods, to reveal the principles underneath. In this project, using high-throughput surface plasmon resonance (SPR) technology, we will study the binding affinity and kinetics of nanoparticles (with different physicochemical parameters and surface functional groups) with a variety of proteins (plasma proteins, surface receptor proteins from phagocytic cells and surface specific receptor proteins from tumor cells) under various conditions, and correlate these results with the corresponding cell uptake, to elucidate the effect of physicochemical parameters and surface functional groups on the interaction between nanoparticles and proteins, and to reveal the mechanism of the protein corona formation and cellular uptake of nanoparticles. In the meantime, with the aid of the high-through method, we will explore the interaction between nanomaterials and non-protein biomolecules to find new bioeffects and new phenomena.

阐明纳米材料与生物系统相互作用的分子机制对纳米材料的生物安全性评价及生物医学应用至关重要。因此，纳米粒子与蛋白质相互作用成为当前国际上的热门研究领域。然而目前大多数工作缺乏系统性，一些结果甚至相互矛盾，无法得到普遍性规律。因此亟需通过高通量的研究方法，系统地研究不同纳米粒子与大量蛋白质在多种不同条件下的相互作用规律。本项目拟采用基于表面等离子共振(SPR)的高通量技术，系统研究具有不同理化参数和功能基团的多种纳米粒子与多种蛋白质(血浆蛋白，吞噬细胞及肿瘤细胞的表面特异受体蛋白)在多种条件下的结合热力学和动力学规律，并与细胞摄取等生物效应相关联，系统阐明纳米粒子的理化参数和功能基团对其与蛋白质相互作用、纳米粒子蛋白冠的形成的影响规律，及纳米粒子的细胞摄入等生物效应的分子机制。同时，借助建立的高通量方法，开展纳米粒子与非蛋白类生物分子相互作用的前瞻性探索研究，以期发现新的生物效应分子或新现象。