Develop hybrid optical-magneto nanoprobes for tracking dendritic cells

开发用于跟踪树突状细​​胞的混合光磁纳米探针

• 批准号: 7642123
• 负责人: DMITRY S KOKTYSH
• 金额: $ 7.75万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7642123
• 关键词: Amines; Area; Basic Science; Biocompatible; Biological Assay; CD80 gene; Cancer Biology; Cell Membrane Permeability; Cell surface; Cells; Characteristics; Confocal Microscopy; Data; Dendritic Cells; Detection; Development; Dextrans; Disease; Early Diagnosis; Encapsulated; Fluorescence Microscopy; Fluorescence-Activated Cell Sorting; Goals; Hybrids; Image; Imaging Techniques; In Vitro; Label; Libraries; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Membrane; Methods; Mind; Modality; Multimodal Imaging; Optics; Pattern; Penetration; Population; Process; Property; Quantum Dots; Resolution; Route; Semiconductors; Speed; Staging; Techniques; Transgenic Mice; Work; cell motility; clinical application; crosslink; data acquisition; dextran; experience; imaging modality; imaging probe; improved; in vivo; information gathering; iron oxide; migration; molecular imaging; mouse model; nanoparticle; nanoprobe; novel; optical imaging; public health relevance; quantum; research study; success; trend; water solubility

DESCRIPTION (provided by applicant): In the past decade, we have witnessed tremendous advances in the development and implementation of non- invasive molecular imaging in order to phenotypically characterize cancers through early detection, staging using molecular imaging. Among these techniques, optical and magnetic resonance (MR) imaging modalities have evolved with remarkable speed. This approach has revolutionized the way we detect the diseases in both basic research and clinical applications. Despite its recent success however, experiences obtained from these works has led us to believe that there is no single imaging modality which can effectively provide information that is sufficiently robust to detect small populations of cells through highly sensitive and deep penetration and with the capability of quick data acquisition and processing. Therefore, the current trend in this area attempts to combine the imaging modalities necessary to provide superior imaging properties through synergistic enhancements unmatched by any single modality. In this application, we propose to develop a novel hybrid imaging nanoprobe (HINP) for high resolution imaging of dendritic cells (DCs) using MR-optical imaging techniques. The HINP consists of near-infrared (NIR) emitting semiconductor quantum dots (QDs) tethered to superparamagnetic iron oxide (SPIO) nanoparticles. Further, we plan to modify this hybrid probe to generate a membrane-permeable derivative for tracking the migration of DCs in vivo. In our preliminary experiments, we synthesized a library of QDs with suitable characteristics for in vivo imaging, including water solubility, stability, precisely tunable NIR emissions and high quantum yields (30-70%). The dextran cross-linked negative contrast SPIO nanoparticles have also been developed. Our hypothesis is that, if developed, this hybrid imaging nanoprobe could be used to track the migration patterns of DCs in a mouse model using optical and MR imaging techniques. Additionally, we want to optimize the sensitivity of DCs migration detection via HINP and improve the distribution route of these immunological cells. PUBLIC HEALTH RELEVANCE: Hybrid imaging nanoprobes from semiconductor quantum dots and superparamagnetic iron oxide nanoparticles will be developed for cumulative enhancing both optical and magnetic resonance imaging techniques capabilities. This multimodal imaging strategy will extend our current understanding of cancer biology.

描述（由申请人提供）：在过去的十年中，我们目睹了非侵入性分子成像的开发和实施方面的巨大进步，以便通过早期检测来表型地表征癌症，并使用分子成像进行分期。在这些技术中，光学和磁共振（MR）成像方式以显着的速度发展。这种方法彻底改变了我们检测基础研究和临床应用中疾病的方式。尽管从这些作品中获得的经验最近取得了成功，但仍使我们相信没有单一的成像方式可以有效地提供足够强大的信息，可以通过高度敏感和深层渗透以及快速数据获取和处理的能力来检测细胞的少量。因此，该领域的当前趋势试图结合所需的成像方式，以通过任何单个模态无与伦比的协同增强功能提供出色的成像性能。在此应用中，我们建议使用MR光学成像技术开发一种新型的混合成像纳米探针（HINP），以对树突状细胞（DC）进行高分辨率成像。 HINP由近红外（NIR）发射的半导体量子点（QD）束缚于超帕磁铁氧化铁（SPIO）纳米颗粒。此外，我们计划修改该混合探针，以生成用于跟踪体内DC迁移的膜渗透导数。在我们的初步实验中，我们合成了一个具有适合体内成像特征的QD库，包括水溶性，稳定性，准确的可调NIR排放和高量子产率（30-70％）。还已经开发了葡聚糖交联的阴性对比度纳米颗粒。我们的假设是，如果开发了这种混合成像纳米探针，则可以使用光学和MR成像技术在小鼠模型中跟踪DC的迁移模式。此外，我们希望通过HINP优化DCS迁移检测的灵敏度，并改善这些免疫细胞的分布途径。公共卫生相关性：将开发出来自半导体量子点和超顺磁铁氧化铁纳米颗粒的混合成像纳米探针，以累积增强光学和磁共振成像技术的能力。这种多模式成像策略将扩展我们当前对癌症生物学的理解。