Nanoparticle Intervention in Cell Behavior

纳米颗粒干预细胞行为

• 批准号: 9900842
• 负责人: Catherine J. MURPHY
• 金额: $ 29.95万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900842
• 关键词: 3-Dimensional; Adsorption; Affect; Alzheimer' s Disease; Artificial nanoparticles; Behavior; Binding; Binding Proteins; Bioavailable; Biological; Cell Communication; Cell physiology; Cells; Chemistry; Chemotactic Factors; Colloids; Diagnostic Imaging; Dose; Drug Delivery Systems; Environment; Epitopes; Expression Profiling; Future; Gene Expression; Hydrophobicity; In Vitro; Incubated; Intervention; Lead; Libraries; Ligands; Light; Lipids; Liquid substance; Literature; Measurement; Measures; Membrane; Methods; Molecular; Molecular Conformation; Motion; Neurodegenerative Disorders; Nucleic Acids; Optics; Parkinson Disease; Property; Protein Conformation; Proteins; Proteomics; Reporting; Rupture; Sampling; Signal Transduction; Solvents; Surface; Techniques; Testing; Therapeutic; Vesicle; Work; biological adaptation to stress; biophysical techniques; cell behavior; cell motility; cell type; colloidal nanoparticle; design; endoplasmic reticulum stress; exosome; experimental study; extracellular vesicles; imaging agent; improved; intercellular communication; interest; learning materials; migration; misfolded protein; nanoGold; nanoparticle; nanoparticle exposure; programs; protein aggregation; response; successful intervention; van der Waals force

Nanoparticle Intervention in Cell Behavior: Summary/Abstract Colloidal nanoparticles (NPs) are of great interest as diagnostics, imaging agents, drug delivery vehicles, and therapeutics. Gold NPs are an important class of these materials due to their brilliant optical and photothermal properties. Most NP-cell studies focus on NP killing or targeting (with surface ligands) various cells, although recent controversies in the literature suggest that targeting does not work. Gene expression profiles of various cells, as a function of NP dose, are commonly reported. Still unanswered is the question of exactly how, at the molecular level, NPs affect cellular behavior and cellular function, especially in the absence of (or biomolecular corona covering up of) targeting ligands. The three Specific Aims below propose three different mechanisms of how NPs can intervene in cell behavior, across a variety of cell types to show generality. In Aim 1, the hypothesis is that NPs sequester biomolecules from the cellular milieu, making these biomolecules less bioavailable to the cell and thereby alter cellular behavior. The experiments in this Aim focus on cellular migration as a function of chemoattractant concentration in three-dimensional matrices; measurements of cellular migration ability as a function of chemoattractant loss via adsorption to NPs will be undertaken. In Aim 2, the hypothesis is that cellular unfolded protein response to NP exposure is directly correlated to the amount of unfolded proteins that the NPs display on their surfaces. The experiments in this Aim focus on a mass spectral footprinting technique to infer protein display on NP/biological samples that are known to upregulate, or not upregulate, the unfolded protein response in cells. In Aim 3, the hypothesis is that NPs bind to exosomes, small extracellular vesicles that are believed to be important in intercellular communication. The experiments in this Aim focus on in vitro measures of exosome binding or bursting to a library of nanoparticles.!

纳米粒子干预细胞行为：总结/摘要 胶体纳米粒子 (NP) 作为诊断剂、显像剂、药物而受到极大关注 运载工具和疗法。金纳米颗粒是此类材料中的一类重要材料 由于其出色的光学和光热特性。大多数 NP 细胞研究集中于 NP 杀死或靶向（使用表面配体）各种细胞，尽管最近存在争议 文献中表明目标定位不起作用。基因表达谱 各种细胞作为 NP 剂量的函数，已被广泛报道。仍然没有答案的是 纳米粒子到底如何在分子水平上影响细胞行为和细胞的问题 功能，特别是在没有靶向（或生物分子冠覆盖）的情况下 配体。下面的三个具体目标提出了 NP 的三种不同机制 可以干预细胞行为，在多种细胞类型中表现出通用性。在目标 1 中， 假设是纳米粒子从细胞环境中隔离生物分子，使这些 生物分子对细胞的生物利用度较低，从而改变细胞行为。这 该目的的实验重点关注作为化学引诱剂功能的细胞迁移 三维矩阵中的浓度；细胞迁移能力的测量 作为通过吸附到纳米粒子上的化学引诱剂损失的函数将被进行。在目标 2 中， 假设细胞未折叠蛋白对 NP 暴露的反应直接 与纳米粒子在其表面展示的未折叠蛋白质的数量相关。 本目标中的实验侧重于质谱足迹技术来推断 已知上调或不上调的 NP/生物样品上的蛋白质展示， 细胞中未折叠的蛋白质反应。在目标 3 中，假设 NP 结合 外泌体，小细胞外囊泡，被认为在细胞间质中很重要 沟通。该目的的实验重点是外泌体的体外测量 结合或爆发到纳米粒子库。！