Monovalent Nanocrystals for Biomedical Imaging

用于生物医学成像的单价纳米晶体

• 批准号: 7707451
• 负责人: PAUL Damien ADAMS
• 金额: $ 21.3万
• 依托单位: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707451
• 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

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）：提出方法来开发用于合成无毒量子点的有效和通用程序，以及用于将这些点缀合或“标记”到蛋白质，以增强和改进生物医学成像技术。人们普遍认为，在蛋白质标记和其他成像技术的应用中，量子点（QD）比有机染料或金纳米晶体具有许多优势。通过成像技术进行疾病检测的方法需要量子点与生物分子结合的新方法。拟议的项目涉及具有有机合成（制备用于钝化和稳定纳米晶体的定制树枝状分子）、纳米晶体合成（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（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的可行性）和单分子光谱（以证明设计的系统有助于蛋白质折叠的研究）。该团队将开发技术来表征纳米晶体生物共轭物先前未实现的结构和/或生物特性，以及随后的体内特性。该项目目标的实现预计将展示生物纳米技术作为诊断和治疗新途径的优势。该探索性项目有 3 个具体目标： 1. 合成、表征和优化适当功能化的树枝状分子，用于连接无毒的 Mn 掺杂 ZnSe (Mn:ZnSe d-dots) 和 InAs/InP/ZnS 核/壳/壳近红外 (NIR) ) QD。 2.探索固相合成策略来制备共价连接到聚合物树脂上的Mn:ZnSe d-点。使用甲氧基乙胺封端的树枝状聚合物衍生量子点的水溶性。 3. 通过四个接头对用于蛋白质缀合的单价 d-点进行功能化，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。 公共健康相关性：有机染料已在生物医学成像应用中使用多年，但它们存在许多限制，其中许多限制可以通过使用纳米尺寸晶体（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，包括市售纳米晶体材料的重金属成分的毒性、无毒量子点的合成方法以及将量子点与蛋白质等生物分子偶联的低效方法。指导该项目的阿肯色大学团队旨在克服这些限制，并且具有独特的资格，因为该团队的主要研究人员在蛋白质偶联无毒量子点的合成和评估的各个方面都具有专业知识。