Hybrid nanomaterials for dynamic, intracellular radioisotope detection

用于动态细胞内放射性同位素检测的混合纳米材料

• 批准号: 8854082
• 负责人: CRAIG A ASPINWALL
• 金额: $ 18.46万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8854082
• 关键词: Antibodies; Area; Beta Particle; Binding; Binding Proteins; Biological; Biological Assay; Caliber; Carbohydrates; Categories; Cells; Chemicals; Clinical; Collection; Deposition; Detection; Development; Diffusion; Disease; Dyes; Elements; Environment; Geometry; Glucose; Gray unit of radiation dose; Half-Life; Health; Human; Hybrids; Image; Integral Membrane Protein; Intracellular Transport; Investigation; Isotopes; Label; Lead; Life; Ligands; Liquid substance; Membrane Lipids; Modeling; Molds; Molecular; Molecular Conformation; Monitor; Nucleic Acids; Optics; Pathway interactions; Penetration; Phytic Acid; Play; Polymers; Prevalence; Proteins; Radioisotopes; Radiolabeled; Research; Research Project Grants; Role; Safety; Sampling; Scintillation Counting; Signal Transduction; Signal Transduction Pathway; Silicon Dioxide; Solubility; Solutions; Surface; System; Techniques; Technology; Thick; Time; Tracer; absorption; analytical tool; aqueous; biological systems; drug discovery; extracellular; human disease; improved; insight; insulin secretion; luminescence; molecular recognition; nanomaterials; novel; particle; radiotracer; reconstitution; research clinical testing; research study; signal processing; small molecule; temporal measurement

DESCRIPTION (provided by applicant): The capability to analyze cellular signal transduction pathways with increasing sensitivity and temporal resolution plays a key role in understanding the underlying molecular pathways involved in human diseases and disorders. Among the most challenging analytes are those present at very low concentrations with high temporal variability and small molecules lacking moieties amenable for optical and/or electrochemical detection. Radioisotopic labels play key roles in the investigation of biological systems in both the research and clinical environments, particularly for small molecule signals derived from carbohydrates. Radioisotopes facilitate highly sensitive detection with minimal perturbation of the analyte, compared to fluorescent labels, etc. Beta-particle emitters, including 32P, 35S, 14C and 3H are commonly used as biological tracers due to the prevalence of these atoms in biological molecules. The most universal radioisotopic label is 3H, due to the ubiquitous presence of H in molecular systems. 3H possesses a number of inherent advantages, including low mass differences between labeled and unlabeled compounds, a reasonable half-life for storage and low energy and short penetration depth that make 3H the safest b-emitting isotope commonly used for biological analysis. Unfortunately, the low energy and short penetration depth also complicate detection of 3H compared to other radioisotopes, minimizing the ability to analyze dynamic signaling processes in single cells or small groups of cells. We propose to develop and characterize a novel core-shell nanomaterial, termed nanoSPA, functionalized with scintillating dyes for sensitive detection of low energy radioisotopes in intracellular environments. This nanomaterial is prepared by depositing a thin silica shell onto a polymer core that is doped with radioisotope- responsive scintillants. The polymer matrix facilitates energy absorption and transfer from the radioisotope to the scintillant dye, whereas addition of the silica shell increass solubility in aqueous samples, and provides an easily modified surface. nanoSPA presents a number of advantages compared to existing technologies, including: a) enhanced compatibility with aqueous samples; b) a high-surface area to volume (SA/V) ratio for improved SPA; c) an easily modified surface for attachment of biomolecules and other chemical species; and d) applicability for intracellular radioisotope imaging. The nanoSPA platform that is proposed herein will provide a key enabling technology in a wide range of applications relevant to human health. Though we will focus our initial, proof-of-concept efforts on assays relevant to glucose-regulated insulin secretion, the range of applications for this technology is extremely broad.

描述（由申请人提供）：分析敏感性和时间分辨率提高的细胞信号转导途径的能力在理解与人类疾病和疾病有关的基本分子途径方面起着关键作用。在最具挑战性的分析物中，有非常低浓度的分析物，具有高时间变异性和缺乏用于光学和/或电化学检测的部分的小分子。放射性病标签在研究生物系统中起关键作用 和临床环境，特别是对于衍生自碳水化合物的小分子信号。与荧光标签等相比，放射性同位素促进了高度敏感的检测，分析物的扰动最小。β粒子发射器，包括32p，35s，14c和3h，通常用作生物学示踪剂，这是由于这些原子在生物分子中的流行。由于分子系统中H无处不在，因此最通用的放射性分析标签为3H。 3H具有许多固有的优势，包括标记和未标记化合物之间的低质量差异，一种合理的存储和低能量的半衰期以及短的渗透深度，使3H成为通常用于生物学分析的最安全的B-发射同位素。不幸的是，与其他放射性同位素相比，低能量和短穿透深度也使3H的检测变得复杂，从而最大程度地降低了分析单细胞或小组细胞中动态信号过程的能力。我们建议开发和表征一种新型的核壳纳米材料，称为纳米传，用闪烁的染料功能化，以对细胞内环境中的低能量放射性同位素进行敏感性检测。该纳米材料是通过将薄的二氧化硅壳沉积到聚合物芯上的，该聚合物芯掺杂了放射性同位素响应式闪烁体。聚合物基质促进了能量吸收，并从放射性同位素转移到闪烁体染料，而添加二氧化硅壳会增加水性样品中的溶解度，并提供易于修饰的表面。与现有技术相比，Nanospa具有许多优势，包括：a）增强与水样样品的兼容性； b）改进水疗中心的高表面区域与体积（SA/V）的比率； c）易于修饰的表面，用于附着生物分子和其他化学物种； d）适用于细胞内放射性同位素成像。本文提出的Nanospa平台将在与人类健康相关的广泛应用中提供关键的启用技术。尽管我们将最初的概念证明工作集中在与葡萄糖调节的胰岛素分泌有关的测定上，但该技术的应用范围非常广泛。

项目成果

Fate of fluorescent core-shell silica nanoparticles during simulated secondary wastewater treatment.

• DOI: 10.1016/j.watres.2015.03.021
• 发表时间: 2015-06-15
• 期刊: WATER RESEARCH
• 影响因子: 12.8
• 作者: Otero-Gonzalez, Lila;Field, Jim A.;Calderon, Isen A. C.;Aspinwall, Craig A.;Shadman, Farhang;Zeng, Chao;Sierra-Alvarez, Reyes
• 通讯作者: Sierra-Alvarez, Reyes