Biological fate and biocompatibility of dendritic and silica-based nanoconstructs

描述(由申请人提供) 本申请是对RFA-ES-06-008：人造纳米材料：生物兼容性和毒性的物理化学原理的响应。纳米技术的最新进展使得制造具有潜在商业和生物医学应用的新型纳米结构成为可能。一些有前景的纳米结构包括树枝状大分子和二氧化硅纳米颗粒。这些纳米结构可以被制造成具有离散的、定义良好的单分散尺寸、形状和表面属性。然而，关于这些颗粒与哺乳动物系统的相互作用，包括它们造成毒性的可能性，人们知之甚少。这一应用的重点是系统地评估树枝状纳米颗粒和二氧化硅纳米颗粒的尺寸、几何形状、孔隙率和表面功能对其毒性和细胞摄取的影响。提出了三个具体目标： 1.树枝状大分子、多孔二氧化硅纳米颗粒和二氧化硅纳米管的制备和表征，这些纳米管具有离散的尺寸、电荷和表面化学变化以调节生物相容性。 2.体外评价制备的纳米材料的毒性、生物相容性和吸收机制随物理化学性质的变化。 3.体内评价纳米材料的生物分布和药代动力学，以及它们与物化性质、毒性和生物相容性的相关性。

DESCRIPTION (provided by applicant) This application is in response to the RFA-ES-06-008: Manufactured nanomaterials: Physicochemical principles of biocompatibility and toxicity. Recent advances in nanotechnology have enabled fabrication of novel nanoconstructs with potential commercial and biomedical applications. Some promising nanoconstructs include dendrimers and silica nanoparticles. These nanoconstructs can be fabricated with discrete, well-defined monodisperse size, shape and surface properties. However little is known about the interactions of these particles with mammalian systems including their potential to cause toxicity. The focus of this application is on systematically evaluating the influence of size, geometry, porosity and surface functionality of dendritic as well as silica nanoparticles on their toxicity and cellular uptake. Three Specific Aims are proposed: 1. Preparation and characterization of dendrimers, porous silica nanoparticles, and silica nanotubes with discrete variations in size, charge and surface chemistry to regulate biocompatibility. 2. In vitro evaluation of toxicity, biocompatibility and mechanisms of uptake of the prepared nanomaterials as a function of physicochemical properties. 3. In vivo evaluation of biodistribution and pharmacokinetics of the nanomaterials and their subsequent correlation with physicochemical properties, toxicity and biocompatibility.