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Monovalent Nanocrystals for Biomedical Imaging

用于生物医学成像的单价纳米晶体

基本信息

批准号：
7904025
负责人：
PAUL Damien ADAMS
金额：
$ 17.57万
依托单位：
UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
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：
2009-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7904025
关键词：
Area Arkansas Biochemistry Biological Cadmium Collaborations Coupling Dendrimers Detection Development Diagnostic Disease Dyes Electronics Evaluation Future Goals Gold Heavy Metals Imaging Techniques Imaging technology In Vitro Ligands Ligation Maleimides Methodology Methods Nitrilotriacetic Acid Organic Synthesis Plant Resins Polymers Preparation Principal Investigator Procedures Property Protein Chemistry Proteins Qualifying Quantum Dots Research Research Personnel S Phase Semiconductors Signal Transduction Solid Spectrum Analysis System Techniques Technology Therapeutic Toxic effect Universities Water bioimaging design experience flexibility improved in vivo indium arsenide nanobiotechnology nanocrystal nanoscale novel physical property protein folding public health relevance single molecule stoichiometry technique development water solubility

项目摘要

DESCRIPTION (provided by applicant): Methodology is proposed to develop efficient and general procedures for the synthesis of nontoxic quantum dots, and for conjugating, or 'tagging' these dots to proteins, for the purpose of enhancing and improving biomedical imaging techniques. It is generally agreed that quantum dots (QDs) offer many advantages over organic dyes or gold nanocrystals in applications of protein tagging and other imaging technologies. Approaches to disease detection via imaging techniques require novel methods of QD conjugation to biomolecules. The proposed project involves a collaboration between Principal Investigators with expertise in organic synthesis (to prepare tailored dendrons for use in passivating and stabilizing nanocrystals), nanocrystal synthesis (to design and synthesize nontoxic nanocrystals with tunable electronic and spectroscopic properties), physical biochemistry (to demonstrate the feasibility of attachment of the designed nanocrystals to a representative protein that is involved in cell signaling), and single molecule spectroscopy (to demonstrate the ability of the designed systems to aid in the study of protein folding). The team will develop techniques to characterize previously unrealized structural and/or biological properties of nanocrystal bioconjugates in-vitro, and subsequently in-vivo. Accomplishment of the aims of this project is expected to demonstrate the advantages of bionanotechnology as a new avenue of diagnostic and therapeutic treatment. This exploratory project has 3 specific aims: 1. Synthesize, characterize, and optimize appropriately functionalized dendrons for ligation to nontoxic Mn-doped ZnSe (Mn:ZnSe d-dots) and InAs/InP/ZnS core/shell/shell near infrared (NIR) QDs. 2. Explore solid-phase synthesis strategies to prepare Mn:ZnSe d-dots that are covalently attached to polymer resins. Derivatize the quantum dots for water solubility using methoxyethylamine-capped dendrimers. 3. Functionalize the monovalent d-dots for protein conjugation via four linkers that will provide maximum potential in a wide variety of protein applications: nitrilotriacetic acid (NTA), N-hydroxysuccinimide (NHS), maleimide, and acyl hydrazide. Conjugate the d-dots with representative proteins, purify, and characterize chemically and spectroscopically. PUBLIC HEALTH RELEVANCE: Organic dyes have been used for years in biomedical imaging applications, but they suffer from a number of limitations, many of which can be overcome by using nanometer-sized crystals (nanocrystals, also known as quantum dots). Past efforts in this area have several drawbacks, including toxicity from the heavy metal components of commercially available nanocrystalline materials, methods for the synthesis of nontoxic quantum dots, and inefficient methods for coupling quantum dots to biomolecules such as proteins. The University of Arkansas team directing this project aims to overcome these limitations, and is uniquely qualified to do so, since it comprises Principle Investigators with expertise in every aspect of the synthesis and evaluation of protein-coupled nontoxic quantum dots.

描述（由申请人提供）：为了增强和改进生物医学成像技术的目的，提出方法学以开发用于合成无毒量子点以及用于将这些量子点缀合或“标记”到蛋白质的有效和通用程序。人们普遍认为，量子点（QD）在蛋白质标记和其他成像技术的应用中提供了许多优于有机染料或金纳米晶体的优点。通过成像技术进行疾病检测的方法需要QD与生物分子缀合的新方法。拟议的项目涉及在有机合成专业知识的主要研究者之间的合作（以制备用于钝化和稳定纳米晶体的定制树枝化基元），（设计和合成具有可调电子和光谱特性的无毒纳米晶体），物理生物化学（为了证明将设计的纳米晶体附着到参与细胞信号传导的代表性蛋白质上的可行性），和单分子光谱学（以证明所设计的系统有助于研究蛋白质折叠的能力）。该团队将开发技术来表征以前未实现的结构和/或生物特性的生物共轭物在体外，随后在体内。该项目目标的实现有望展示生物纳米技术作为诊断和治疗新途径的优势。这个探索性项目有三个具体目标：1。合成、表征和优化适当官能化的树枝状分子，用于连接到无毒Mn掺杂的ZnSe（Mn：ZnSe d点）和InAs/InP/ZnS核/壳/壳近红外（NIR）QD。2.探索固相合成策略以制备共价连接到聚合物树脂的Mn：ZnSe d-点。使用甲氧基乙胺封端的树枝状聚合物将量子点衍生化以获得水溶性。3.通过四个连接体将单价d-点功能化用于蛋白质缀合，这将在各种蛋白质应用中提供最大潜力：次氮基三乙酸（NTA）、N-羟基琥珀酰亚胺（NHS）、马来酰亚胺和酰基酰肼。将d点与代表性蛋白质结合，纯化，并进行化学和光谱表征。公共卫生关系：有机染料已在生物医学成像应用中使用多年，但它们受到许多限制，其中许多可以通过使用纳米尺寸的晶体（纳米晶体，也称为量子点）来克服。过去在这一领域的努力有几个缺点，包括来自市售纳米晶材料的重金属组分的毒性，用于合成无毒量子点的方法，以及用于将量子点偶联到生物分子（如蛋白质）的低效方法。指导该项目的阿肯色州大学团队旨在克服这些限制，并且是唯一有资格这样做的，因为它包括在蛋白质偶联无毒量子点的合成和评估的各个方面具有专业知识的主要研究人员。