纳米材料进入血液后，表面会立即吸附大量蛋白；低密度脂蛋白(LDL)是吸附蛋白的组分之一，其结构与性质改变很可能诱导动脉粥样硬化。因此，在纳米安全性评价方面，纳米材料与LDL作用及其心血管效应研究具有重要意义。本项目拟在纳米-生物界面、分子、细胞等不同层面，研究碳类与金属类纳米材料与LDL作用过程及其潜在心血管效应。首先，结合X射线液体界面分析、同步辐射成像与原位谱学、电子顺磁共振谱等方法，研究纳米材料与LDL的界面作用，揭示纳米材料调控LDL聚集与融合、诱导脂质过氧化的物理化学机制；然后，在分子与细胞水平，研究纳米材料-LDL复合物的心血管效应及其生物学机制；最终，揭示纳米材料理化性质如何调控LDL物理结构与化学性质、进而诱导心血管效应的构-效关系。本项目将发展针对纳米-生物界面作用的创新分析方法，阐明纳米材料与脂蛋白作用的生物学效应与物理化学机制，为纳米安全性评价提供关键科学依据。

Proteins will adsorb on the surface of nanomaterials (NMs) when they enter into blood flow. Low density lipoprotein (LDL) is a type of protein with high abundance in the blood and probably induce atherosclerosis when the structure and chemical properties change. It is thus significant to study how NMs interact with LDL and the subsequent cardiovascular risks to human health. In this proposal, we plan to study pro-/anti-atherosclerotic potential by the complex of LDL with carbon NMs and metal NMs at nano-bio interface and the molecular and cellular levels. At first, combining electron spin resonance spectroscopy with synchrotron radiation techniques including X-ray liquid interface analysis and X-ray fluorescence (XRF) nanoprobe imaging with X-ray absorption near edge structure (XANES), we will capture the change in the interfacial structures between NMs and the major components of LDL such as phospholipids, cholesterol, and apolipoprotein. We will then reveal how NMs mediate the fusion and aggregation of LDL and how NMs induce chemical reactions that promotes the oxidation of LDL. Secondly, we will study potential pro-cardiovascular effects of NM-LDL complex at the molecular and cellular levels and uncover the biological mechanism. Finally, we will demonstrate the structure-effect relationship between the physicochemical properties of NMs and the structural of LDL and its properties which correlates to the following pro-atherosclerotic effects. In this work, we will develop important methods to characterize nano-bio interface that paves the ways for studying NM-lipoprotein interaction in future. The method is significant to illustrate biological effects of NM-lipoprotein complex and its potential mechanism. Moreover, the study about the pro-atherosclerotic potential of NMs will provide crucial evidences for the safety evaluation of NMs.