Biological Fate and Biocompatability of Dendritic and Silica-Based Nanoconstructs

描述(申请人提供)：该项目的全球目标是评估纳米材料的物理化学特性如何调节生物环境响应。在这一应用中，将检测二氧化硅纳米颗粒(SNPs)的孔隙率、降解和曲率对细胞摄取、生物分布、药代动力学和毒性的影响。具体地说，我们将更详细地研究SNPs的细胞命运和细胞内运输机制，如何启动炎症反应来响应物理化学性质的变化，以及SNPs降解产物的生物命运。提出了三个具体的目标：1)合成和表征大小、孔隙率、表面粗糙度和功能以及生物可降解性存在系统差异的SNPs；2)研究表面性质如何在体外影响蛋白质和细胞炎症介导机制；3)研究体内慢性炎症介导机制。

DESCRIPTION (provided by applicant): The global goal of this project is to assess how physicochemical characteristics of nanomaterials modulate biological environmental responses. In this application the influence of porosity, degradation and curvature of silica nanoparticles (SNPs) on mechanisms of cellular uptake, biodistribution, pharmacokinetics and toxicity will be examined. Specifically, we will examine in more detail the cellular fate and mechanisms of intracellular transport of the SNPs, how inflammatory responses are initiated in response to the changes in the physicochemical properties, and what would be the biological fate of degradation products of SNPs. Three Specific Aims are proposed: 1) 1. Synthesis and characterization of SNPs with systematic differences in size, porosity, surface roughness and functionality, and biodegradability, 2) Investigate how surface properties affect protein and cellular inflammatory mediated mechanisms in vitro, 3) Investigate chronic inflammatory mediated mechanisms as a function of surface properties in vivo.