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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

基本信息

批准号：
7860543
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
项目类别：
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/7860543
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

项目摘要

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，我们已经见证了非侵入性分子成像的开发和实施的巨大进步，以通过使用分子成像的早期检测、分期来表征癌症的表型。在这些技术中，光学和磁共振（MR）成像模式已经以惊人的速度发展。这种方法彻底改变了我们在基础研究和临床应用中检测疾病的方式。尽管最近取得了成功，但是从这些工作中获得的经验使我们相信，没有单一的成像方式可以有效地提供足够稳健的信息，以通过高灵敏度和深穿透并具有快速数据采集和处理的能力来检测小细胞群体。因此，该领域的当前趋势试图通过任何单一模态都无法比拟的协同增强来联合收割机组合提供上级成像特性所必需的成像模态。在本申请中，我们提出开发一种新型的混合成像纳米探针（HINP），用于使用MR光学成像技术对树突状细胞（DC）进行高分辨率成像。HINP由近红外（NIR）发射半导体量子点（QD）和超顺磁性氧化铁（SPIO）纳米颗粒组成。此外，我们计划修改这个混合探针，以产生一个膜渗透性的衍生物，用于跟踪在体内的DC的迁移。在我们的初步实验中，我们合成了具有适合体内成像特性的QD库，包括水溶性、稳定性、精确可调的NIR发射和高量子产率（30-70%）。还开发了葡聚糖交联的负对比SPIO纳米颗粒。我们的假设是，如果开发出来，这种混合成像纳米探针可用于使用光学和MR成像技术跟踪小鼠模型中DC的迁移模式。此外，我们希望通过HINP优化DC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：将开发来自半导体量子点和超顺磁性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目前对癌症生物学的理解。