Monovalent Nanocrystals for Biomedical Imaging

用于生物医学成像的单价纳米晶体

• 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
• 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; 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）：提出了方法来开发合成无毒量子点的有效和一般程序，以及将这些点共轭或将这些点“标记”到蛋白质上，以增强和改善生物医学成像技术。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具有许多优势或有机染料或金纳米晶体的优势。通过成像技术检测疾病检测方法需要新颖的QD结合方法与生物分子。 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参与细胞信号传导的代表性蛋白质和单分子光谱（证明设计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纳米晶体生物缀合物的先前未实现的结构和/或生物学特性，随后在体内。预计该项目目标的实现将证明Bionanotechnology的优势是诊断和治疗治疗的新途径。该探索性项目具有3个具体目的：1。合成，表征和优化适当功能化的树突，以连接无毒的Mn掺杂ZnSe（MN：ZNSE D-DOTS）和INAS/INAS/INP/INP/INP/INP/INP/INP/ZNS CORE/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL/SHELL SELL RACE BRACRARERARED（NIR）QDS。 2。探索固相合成的策略，以准备MN：ZnSE D点，这些ZnSE D点与聚合物树脂共同附着。使用甲氧亚胺限制的树枝状聚合物衍生量子点以使其溶解度。 3.通过四个接头功能化蛋白质共轭的单价D点，这些接头将在多种蛋白质应用中提供最大潜力：硝基二酸（NTA），N-羟基糖糖酰亚胺（NHS），马来酰亚胺，马来酰亚胺和乙酰氢氮杂。将D点与代表性蛋白结合在一起，纯化并在化学和光谱上表征。 公共卫生相关性：有机染料已多年用于生物医学成像应用，但它们遭受了许多局限性，其中许多可以通过使用纳米尺寸晶体（纳米晶体（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件的毒性，无毒量子点的合成方法以及将量子点与生物分子（如蛋白质）偶联的方法。指挥该项目的阿肯色大学团队旨在克服这些局限性，并且具有独特的资格，因为它包括主要研究者在蛋白质偶联的无毒量子点的合成和评估方面具有专业知识的主要研究者。