Cell-and Nucleus-Permeable Luminescent Gold Nanoparticles

描述(申请人提供)：细胞内成像和靶向递送需要新的纳米材料，这种材料可以直接穿过细胞膜进入胞浆，而不需要被膜结合的囊泡包裹。我们最近发现，直径约2 nm的高发光金纳米粒子暴露在HeLa细胞中时，明显通过被动扩散迅速穿过细胞膜和核膜，随后结合到活细胞的染色体上。这项申请的目的是解开支配纳米材料细胞/核渗透性的基本原理。为了实现这一目标，我们建议开发通用的方法，使我们能够创建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在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大到本探索期以外的范围，并导致用于细胞内成像和靶向递送的新纳米药物的开发。 与公共健康相关：细胞和细胞核可穿透发光的金纳米粒子纳米材料通常不能通过被动扩散穿过细胞/核膜，但通过内吞作用被细胞摄取。我们最近发现，发光的金纳米结构可以在几分钟内直接扩散到细胞和核膜上。我们建议开发一个具有不同表面性质的发光金纳米探针库，这样我们就可以揭示控制金纳米颗粒细胞和核渗透性的潜在原理。1

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