Nanoparticle Intervention in Cell Behavior

纳米粒子干预细胞行为：摘要/摘要 胶体纳米颗粒（NP）作为诊断剂、成像剂、药物组合物和药物组合物是非常令人感兴趣的。 递送载体和治疗剂。金纳米颗粒是这些材料中的重要一类 因为它们具有出色的光学和光热性能。大多数NP细胞研究集中在 NP杀伤或靶向（与表面配体）各种细胞，虽然最近的争议 在文献中表明，目标不起作用。基因表达谱 通常报道各种细胞作为NP剂量的函数。仍然没有答案的是， 在分子水平上，NP究竟如何影响细胞行为和细胞功能的问题。 功能，特别是在没有（或生物分子冠覆盖）靶向的情况下 配体。下面的三个具体目标提出了三种不同的机制， 可以干预细胞的行为，跨越各种细胞类型，以显示通用性。在目标1中， 假设是纳米颗粒从细胞环境中隔离生物分子， 生物分子对细胞的生物利用度较低，从而改变细胞行为。的 本目标中的实验集中于作为化学引诱物的函数的细胞迁移 三维基质中的浓度;细胞迁移能力的测量 作为通过吸附到NP的化学引诱物损失的函数。在目标2中， 假设细胞未折叠蛋白对NP暴露的反应是直接的 与纳米颗粒表面展示的未折叠蛋白质的量相关。 本目标中的实验集中在质谱足迹技术上，以推断 NP/生物样品上的蛋白质展示已知上调，或不上调， 细胞中未折叠的蛋白质反应。在目标3中，假设是NP结合至 外泌体，小的细胞外囊泡，被认为是重要的细胞间 通信该目的中的实验集中于外泌体的体外测量。 结合或爆发到纳米粒子库中。

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.!