单一表面理化性质渐变的金纳米颗粒库对树突状细胞免疫功能的调节及机制研究

树突状细胞(DCs)是机体功能最强的专职抗原递呈细胞，在启动免疫应答和介导免疫耐受过程中发挥关键作用。研究纳米材料对DCs免疫功能的调节是纳米材料免疫效应研究的重要组成部分。尽管已有研究表明纳米材料的表面修饰影响DCs的免疫功能，但目前的研究局限于对其个别理化性质的探索，缺乏纳米材料表面理化性质与DCs免疫功能之间关联的系统性研究。本课题组的初期研究发现，表面疏水性渐变的金纳米颗粒差异调节正常条件和LPS诱导条件下小鼠骨髓来源树突状细胞（BMDCs）的成熟。在此基础上，本课题拟以BMDCs为树突状细胞模型，在有或无LPS的条件下，筛选单一表面理化性质包括电荷、亲疏水性、π键、氢键及拓扑结构渐变的金纳米颗粒库，获得能够调节BMDCs免疫功能的金纳米颗粒，运用细胞及分子生物学的技术和方法，系统研究纳米颗粒表面理化性质对BMDCs免疫功能的调节及其规律，阐明相关分子机制。

As the most potent antigen presenting cells, dendritic cells (DCs) play key roles in the initiation of immune responses and tolerance induction. To evaluate the immunological effect of nanomaterials on DCs is a vital component of the immunological effect of nanoparticles. Recent reports showed that the surface modification modulated the immune function of DCs, however, those researches were restricted to certain individual physicochemical properties. It is urgently needed to investigate the correlation between the surface physicochemical properties and its immunological effects systematically. Our preliminary data showed that the gold nanoparticles (AuNPs) with a gradient change in surface hydrophobicity differently modulated the maturation of mouse bone marrow-derived dendritic cells (BMDCs) under normal or inflammatory conditions induced by lipopolysaccharides (LPS). Based on that, we will use BMDCs as model cells to screen the AuNP library with a univariant gradient change in physicochemical properties including surface charge, hydrophobicity, H-bonding, π-bonding and topology, to obtain the AuNPs that can modulate the maturation of BMDCs in the presence or absence of LPS. Using cellular and molecular biological techniques, we will explore the immunomodulation of BMDCs by AuNPs systematically and elucidate the molecular mechanisms involved.