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Superior Near-IR Dyes for Bioimaging

用于生物成像的优质近红外染料

基本信息

批准号：
7611638
负责人：
Brian David Gray
金额：
$ 17.68万
依托单位：
MOLECULAR TARGETING TECHNOLOGIES, INC.
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：
2009-07-15 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7611638
关键词：
Affinity Alkanesulfonates Amines Animals Antibodies Biological Biological Assay Biotechnology Biotin Cartoons Chemical Structure Chemicals Clinical Collaborations Complement Cultured Cells Cysteine Data Development Devices Diagnostic Dyes Encapsulated Esters Evaluation Exhibits Extinction (Psychology)Fluorescence Fluorescence Microscopy Fluorescent Dyes Fluorescent Probes Folate Folic Acid Derivative Gel Goals Hemoglobin Hormones Image Imaging technology Immunoglobulin G In Vitro Infrared Rays Investigation Label Left Life Ligands Light Medical Medicine Modality Modeling Molecular Molecular Probes Molecular Structure Molecular Target Monitor Mus Operative Surgical Procedures Pathway interactions Patients Performance Pharmaceutical Preparations Phase Phosphonic Acids Photons Physicians Predisposition Principal Investigator Property Proteins Protocols documentation Research Research Personnel Resolution Rotaxanes Science Series Serum Small Business Innovation Research Grant Solubility Solutions Specificity Staining method Stains Streptavidin Structure System Techniques Technology Tissues Universities Vitamins Water absorption analog aqueous base bioimaging biological systems cancer imaging cyanine cyanine dye cyanine dye 5 folate-binding protein gel electrophoresis improved in vivo innovation molecular recognition novel optical imaging professor programs public health relevance quantum sensor squaraine success tumor tumor xenograft

项目摘要

Optical imaging is an advanced technique to image biotechnology products like gels, sensors, and micro arrays. It is also used increasingly to monitor specific molecular pathways in animals. This latter technique uses fluorescent dyes that absorb and emit near-infrared (NIR) radiation (650-900 nm) a spectral window where hemoglobin and water absorb minimally and therefore allow photons to penetrate several centimeters through tissue. This proposal builds on our recent discovery that squaraine rotaxanes (SRs) are among the world's brightest and most stable fluorescent NIR dyes. However due to their poor solubility under aqueous conditions, their usefulness in biological applications remains a challenge thus limiting their commercial appeal. Our plan is therefore to improve dye performance by introducing water solublizing sulfonate or phosphonic acid groups into the molecular structure. With further development, they are likely to become superior replacements for the popular cyanine (Cy5) dyes and become extremely useful probes for both in vitro and in vivo imaging applications. The overall goal for Phase I is to prepare novel water soluble SR dyes and compare the properties of various bioconjugates that have been labeled with SR or Cy5. The two Specific Aims of the present proposal are: 1) SA1 to be performed at MTTI - Synthesize novel water soluble SR NHS esters incorporating multiple sulfonate or phosphonic acid groups and conjugate to 3 different types of biomolecules, an antibody, a protein and a vitamin for comparison with Cy5 analogues. The first goal is to produce water soluble squaraine rotaxane probes having sulfonate or phosphonic acid groups. This will be followed by conjugation of the squaraine rotaxane probes as well as Cy5 as control probe to IgG protein, streptavidin and a folic acid derivative. 2) SA2 to be perfomed at UND - In vitro and in vivo evaluation of bioconjugates. In vitro molecular recognition performance of the SR and Cy5 fluorescent IgG and streptavidin bioconjugates developed at MTTI will be characterized using standard gel electrophoresis and streptavidin/biotin protocols. In vitro and In vivo molecular recognition performance of fluorescent SR and Cy5 folate conjugates will be determined using cultured cells that express high levels of the folate receptor and in whole animal imaging studies of murine xenograft tumor models. The goal is to demonstrate the advantage of using molecular probes labeled with SR dyes in 3 different systems compared with Cy dyes. PA-08-050

光学成像是一种对凝胶、传感器和微阵列等生物技术产品进行成像的先进技术。它还越来越多地用于监测动物的特定分子途径。后一种技术使用吸收和发射近红外 (NIR) 辐射（650-900 nm）的荧光染料，这是血红蛋白和水吸收最少的光谱窗口，因此允许光子穿透组织几厘米。该提案基于我们最近的发现，即方酸轮烷 (SR) 是世界上最亮、最稳定的荧光近红外染料之一。然而，由于它们在水性条件下溶解度差，它们在生物应用中的有用性仍然是一个挑战，从而限制了它们的商业吸引力。因此，我们的计划是通过在分子结构中引入水溶性磺酸盐或膦酸基团来提高染料性能。随着进一步的发展，它们可能成为流行的花青 (Cy5) 染料的优质替代品，并成为体外和体内成像应用中极其有用的探针。第一阶段的总体目标是制备新型水溶性 SR 染料，并比较用 SR 或 Cy5 标记的各种生物结合物的特性。本提案的两个具体目标是： 1) 将在 MTTI 进行 SA1 - 合成新型水溶性 SR NHS 酯，其中包含多个磺酸盐或膦酸基团，并与 3 种不同类型的生物分子、抗体、蛋白质和维生素缀合，以便与 Cy5 类似物进行比较。第一个目标是生产具有磺酸根或膦酸基团的水溶性方酸菁轮烷探针。随后将方酸轮烷探针以及作为对照探针的 Cy5 与 IgG 蛋白、链霉亲和素和叶酸衍生物缀合。 2) SA2 将在 UND 进行 - 生物结合物的体外和体内评估。 MTTI 开发的 SR 和 Cy5 荧光 IgG 以及链霉亲和素生物缀合物的体外分子识别性能将使用标准凝胶电泳和链霉亲和素/生物素方案进行表征。荧光 SR 和 Cy5 叶酸缀合物的体外和体内分子识别性能将使用表达高水平叶酸受体的培养细胞以及小鼠异种移植肿瘤模型的整体动物成像研究来确定。目标是证明在 3 个不同的系统中使用 SR 染料标记的分子探针与 Cy 染料相比的优势。 PA-08-050