Biological fate and biocompatibility of dendritic and silica-based nanoconstructs

树枝状和二氧化硅基纳米结构的生物命运和生物相容性

• 批准号: 7615449
• 负责人: Hamid Ghandehari
• 金额: $ 38.81万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615449
• 关键词: Biodistribution; Biological; Charge; Chemistry; Dendrimers; Drug Kinetics; Evaluation; In Vitro; Nanotechnology; Nanotubes; Porosity; Preparation; Property; Shapes; Silicon Dioxide; Surface; Surface Properties; System; Toxic effect; Variant; base; biomaterial compatibility; in vivo; nanomaterials; nanoparticle; novel; particle; response; size; uptake

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.

描述（由申请人提供） 本申请是为了响应 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。纳米技术的最新进展使得能够制造具有潜在商业和生物医学应用的新型纳米结构。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为具有离散的、明确的单分散尺寸、形状和表面特性。然而，人们对这些颗粒与哺乳动物系统的相互作用（包括它们引起毒性的可能性）知之甚少。 该应用的重点是系统评估树枝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、多孔二氧化硅纳米粒子和二氧化硅纳米管的制备和表征，其尺寸、电荷和表面化学性质离散变化，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作为理化性质的函数。 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。