MECHANISTIC STUDY OF THE CELLULAR MEMBRANE RESPONSE TO SYNTHETIC NANOPARTICLES

细胞膜对合成纳米粒子响应的机制研究

• 批准号: 7609984
• 负责人: GEOFFREY BOTHUN
• 金额: $ 0.85万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609984
• 关键词: Aluminum Oxide; Anesthesia procedures; Benign; Biocompatible Materials; Biological; Cell membrane; Cellular Membrane; Ceramics; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Disruption; Drug Delivery Systems; Engineering; Environmental Risk Factor; Fullerenes; Funding; Grant; Guidelines; Health; Human; Institution; Lipid Bilayers; Location; Measures; Membrane; Membrane Lipids; Modeling; Modification; Molecular; Nanotechnology; Nanotubes; Octanols; Oxides; Partition Coefficient; Property; Research; Research Personnel; Resources; Risk; Safety; Shapes; Source; Surface; System; Techniques; Thermodynamics; Titania; Toxic effect; Transmission Electron Microscopy; United States National Institutes of Health; Visual; Water; Zirconium; cryogenics; design; interest; nanomaterials; nanoparticle; response; size; uptake; zirconium oxide

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A largely unknown aspect of nanotechnology is the interaction between nanomaterials and biological systems. In terms of human health, there are many questions concerning the biological uptake, accumulation, disruption, and potential toxicity of inorganic nanomaterials, specifically synthetic nanoparticles. The myriad of nanoparticle compositions, sizes, shapes, and surface functionalities have made it difficulty to characterize health and environmental risks, and to develop general guidelines for material handling, disposal, and safety. A rationale first step is to examine the interactions between synthetic nanoparticles and cell membranes, which relate to traditional measures of molecular toxicity and anesthesia  the octanol/water partition coefficient. Beginning with the design of lipid bilayers as model cell membranes, a hierarchical experimental approach is used to relate mechanistic information of nanoparticle/membrane interactions in model bilayers to cell membranes. Nanoparticles of particular interest include carbonaceous materials (e.g. fullerenes and nanotubes) and ceramic oxides (e.g. alumina, ceria, titania, and zirconia) with and without chemical surface modification. Cryogenic transmission electron microscopy will be used to examine the degree of association between nanoparticles and lipid membranes, providing visual evidence of accumulation, location, orientation, and nanoparticle-induced morphological changes. Membrane thermodynamic and transport properties are further evaluated using advanced spectroscopic and calorimetric techniques. It is anticipated that this project will aid in the identification of nanoparticle health risks and in the selection and design of biologically and environmentally benign nanomaterials. In addition to the toxicological aspects, information on nanomaterial/cell membrane interactions can be used to create new systems in drug delivery and biomaterials engineering.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 纳米技术的一个很大程度上未知的方面是纳米材料与生物系统之间的相互作用。 就人类健康而言，无机纳米材料（特别是合成纳米颗粒）的生物吸收、积累、破坏和潜在毒性存在许多问题。 纳米颗粒的成分、尺寸、形状和表面功能多种多样，因此很难表征健康和环境风险，也很难制定材料处理、处置和安全的一般准则。 第一步是检查合成纳米粒子和细胞膜之间的相互作用，这与分子毒性和麻醉辛醇/水分配系数的传统测量有关。 从设计脂质双层作为模型细胞膜开始，使用分层实验方法将模型双层中纳米颗粒/膜相互作用的机制信息与细胞膜联系起来。 特别感兴趣的纳米颗粒包括经过或未经化学表面改性的碳质材料（例如富勒烯和纳米管）和陶瓷氧化物（例如氧化铝、二氧化铈、二氧化钛和氧化锆）。 低温透射电子显微镜将用于检查纳米颗粒和脂质膜之间的结合程度，提供积累、位置、方向和纳米颗粒引起的形态变化的视觉证据。 使用先进的光谱和量热技术进一步评估膜的热力学和传输特性。 预计该项目将有助于识别纳米粒子的健康风险以及选择和设计生物和环境友好的纳米材料。 除了毒理学方面之外，纳米材料/细胞膜相互作用的信息还可用于创建药物输送和生物材料工程的新系统。