Cell-and Nucleus-Permeable Luminescent Gold Nanoparticles

描述（由申请人提供）：细胞内成像和靶向递送需要新的纳米材料，这些纳米材料可以直接穿过细胞膜并进入细胞质，而不被膜结合囊泡包裹。我们最近发现，当暴露在HeLa细胞中时，直径约2纳米的高发光金纳米粒子明显通过被动扩散迅速穿过细胞膜和核膜，随后与活细胞中的染色体结合。该应用程序的目的是揭示控制纳米材料的细胞/核渗透性的基本原理。为了实现这一目标，我们提出了一种通用的方法，使我们能够创建一个具有精细表面化学和结构的金纳米探针库，然后应用荧光显微镜技术来研究这些纳米材料的细胞行为。这些目标的成功实现将极大地促进我们对分子水平上调节纳米结构渗透性的基本原理的理解。这些研究将进一步扩展到这个探索期的范围之外，并导致用于细胞内成像和靶向递送的新型纳米药物的开发。

DESCRIPTION (provided by applicant): Intracellular imaging and targeted delivery demand new nanomaterials that can directly cross cell membranes and enter the cytosol without being encapsulated by membrane bound vesicles. We recently found that highly luminescent, gold nanoparticles about 2 nm in diameter when exposed to HeLa cells rapidly crossed cellular membranes and nuclear membranes apparently by passive diffusion and subsequently bound to chromosomes in live cells. The objective of this application is to unravel underlying principles that govern the cell/nuclear permeability of nanomaterials. To achieve this goal, we proposed to develop general approaches that allow us to create a library of gold nanoprobes with fine tuned surface chemistry and structure, and then apply fluorescence microscopy techniques to investigate cell behaviors of these nanomaterials. Successful realization of these aims will greatly advance our understanding of fundamental principles that regulate the permeability of nanostructures at the molecular level. These studies will be further broadened beyond the scope of this exploratory period and lead to development of new nanomedicines for intracellular imaging and targeted delivery. PUBLIC HEALTH RELEVANCE: Cell- and Nucleus-Permeable Luminescent Gold Nanoparticles Nanomaterials generally cannot cross cell /nuclear membranes via passive diffusion, but are taken up by the cell via endocytosis. We recently found a luminescent gold nanostructure can directly diffuse across cell and nuclear membranes within a few minutes. We propose to develop a library of luminescent gold nanoprobes with different surface properties, so that we can uncover the underlying principles that govern cell and nuclear permeability of gold nanoparticles. 1