RELATING BIOMEMBRANE DISRUPTION TO TOX OF SYNTHETIC INORGANIC NANOPARTICLES

生物膜破坏与合成无机纳米颗粒毒性的关系

• 批准号: 7725162
• 负责人: GEOFFREY BOTHUN
• 金额: $ 3.11万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725162
• 关键词: Anesthesia procedures; Behavior; Biological; Biomimetics; Cell membrane; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Consensus; Differential Scanning Calorimetry; Disruption; Electrostatics; Environmental Health; Fluorescence Spectroscopy; Funding; Future; Gold; Government Agencies; Grant; Hybrids; Imagery; Institution; Lipid Bilayers; Lipids; Liposomes; Membrane; Modeling; Molecular; Morphology; Phase; Preparation; Property; Range; Research; Research Personnel; Resources; Risk; Shapes; Silver; Source; Surface; System; Techniques; Therapeutic; Thermodynamics; Titania; Toxic effect; Transmission Electron Microscopy; United States National Institutes of Health; base; cryogenics; fullerene C60; interest; light scattering; nanomaterials; nanoparticle; particle; size; stem; theories; uptake

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. There is growing consensus amongst private, industrial, and government agencies that the potential toxicity of synthetic inorganic nanomaterials must be identified early in order to characterize environmental and health risks and reduce public skepticism. Specific questions have arose concerning the uptake, accumulation, transport, and disruptive effects of nanoparticles in biological systems. Given the wide range of nanoparticle compositions, sizes, shapes, and surface functionalities characterizing toxicity has become a daunting task. The objective of this project is to synthesize biomimetic model cell membranes (i.e. multicomponent lipid bilayers) and conduct mechanistic studies on membrane interactions with synthetic nanoparticles. Conventional theories of toxicity and anesthesia have centered on membrane disruption and molecular partitioning. First, membranes composed of zwitterionic lipids, anionic lipids, and cholesterol will be synthesized via liposome preparation techniques and exposed to native and surface functionalized nanoparticles. Of immediate interest are sub-5 nm titania, C60 fullerene, gold, and silver particles. Changes in membrane thermodynamic and transport properties, such as phase behavior, lipid ordering, and diffusivity, reveal mechanistic information on nanoparticle/membrane interactions stemming from van der Waals, electrostatic, hydrophobic, and undulation forces. Fluorescence spectroscopy and differential scanning calorimetry will be used to evaluate these properties. The influence of interaction mechanisms on membrane morphology will be examined by dynamic light scattering and cryogenic transmission electron microscopy  an extremely powerful visualization technique. In addition to the toxicological information that is expected to be gained from nanoparticle/cell membrane studies, the interaction mechanisms that are revealed will be used in the future to create new nanoparticle-based therapeutics and hybrid bio/nanomaterials.

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。 私人、工业和政府机构日益达成共识，必须尽早识别合成无机纳米材料的潜在毒性，以描述环境和健康风险并减少公众的怀疑。关于纳米颗粒在生物系统中的吸收、积累、运输和破坏作用的具体问题已经出现。鉴于表征毒性的纳米颗粒成分、尺寸、形状和表面功能范围广泛，已成为一项艰巨的任务。该项目的目标是合成仿生模型细胞膜（即多组分脂质双层），并对膜与合成纳米粒子的相互作用进行机制研究。传统的毒性和麻醉理论集中在膜破坏和分子分配上。首先，由两性离子脂质、阴离子脂质和胆固醇组成的膜将通过脂质体制备技术合成，并暴露于天然和表面功能化的纳米颗粒。最令人感兴趣的是 5 nm 以下的二氧化钛、C60 富勒烯、金和银颗粒。膜热力学和传输特性的变化，例如相行为、脂质排序和扩散性，揭示了源自范德华力、静电力、疏水力和波动力的纳米颗粒/膜相互作用的机制信息。荧光光谱和差示扫描量热法将用于评估这些特性。相互作用机制对膜形态的影响将通过动态光散射和低温透射电子显微镜（一种极其强大的可视化技术）进行检查。除了预计从纳米颗粒/细胞膜研究中获得的毒理学信息外，所揭示的相互作用机制将在未来用于创建新的基于纳米颗粒的疗法和混合生物/纳米材料。