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：生物相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新型纳米结构的制造成为可能，具有潜在的商业和生物医学应用。一些有前途的纳米结构包括树枝状聚合物和二氧化硅纳米颗粒。这些纳米结构可以制造成具有离散的、明确定义的单分散尺寸、形状和表面性质。然而，人们对这些颗粒与哺乳动物系统的相互作用知之甚少，包括它们引起毒性的可能性。 本申请的重点是系统地评估树突状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.树枝状聚合物、多孔二氧化硅纳米颗粒和二氧化硅纳米管的制备和表征，其尺寸、电荷和表面化学具有离散变化，以调节生物相容性。 2.根据理化性质对制备的纳米材料的毒性、生物相容性和吸收机制进行体外评价。 3.体内评价纳米材料的生物分布和药代动力学及其与理化性质、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.