Synthesis of Gold Nanoparticle-Cored Dendrimers Linked with Fluorophores and Anti

与荧光团和抗连接物连接的金纳米颗粒核心树枝状聚合物的合成

• 批准号: 8494638
• 负责人: Young Shon
• 金额: $ 10.46万
• 依托单位: CALIFORNIA STATE UNIVERSITY LONG BEACH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494638
• 关键词: Abate; Adverse effects; Antibodies; Area; Basic Science; Biocompatible; Biological; Biological Markers; Biological Sciences; Biology; Biomedical Research; Biotechnology; Cancer Detection; Cancerous; Cells; Chemistry; Clinical; Clinical Research; Complex; Coupling; Cultured Tumor Cells; Data; Data Set; Dendrimers; Development; Diagnostic; Disease; Enhancers; Enrollment; Evaluation; Faculty; Familiarity; Fostering; Funding; Goals; Gold; Heating; Human; Hyperthermia; Image; In Vitro; Information Dissemination; Interdisciplinary Study; Label; Laboratories; Laboratory Research; Life; Ligands; Link; Liquid substance; Malignant Neoplasms; Manuscripts; Medical; Medical Research; Medicine; Methods; Microscopy; Nanostructures; Nanotechnology; Optics; Participant; Performance; Phenotype; Physics; Process; Property; Publishing; Reaction; Research; Research Methodology; Research Personnel; Research Project Grants; Scanning; Science; Scientist; Site; Structure; Students; Surface; System; Techniques; Technology; Technology Transfer; Testing; Therapeutic; Thick; Toxic effect; Translational Research; United States National Institutes of Health; Work; antibody conjugate; base; biomaterial compatibility; cancer cell; cancer diagnosis; cancer therapy; chemotherapy; cytotoxicity; design; experience; fluorescence imaging; fluorophore; graduate student; hyperthermia treatment; interest; killings; macromolecule; meetings; multidisciplinary; nanocarrier; nanomaterials; nanoparticle; nanoparticulate; nanoscience; nanostructured; neoplastic cell; novel; programs; skills; surface coating; tumor; undergraduate student

DESCRIPTION (provided by applicant): Synthesis of Gold Nanoparticle-Cored Dendrimers Linked with Fluorophores and Antibodies: Smart Biomarkers for Cancer Treatments Project Summary Within the last decade, gold nanoparticulate materials have been used increasingly for diverse biological and medical applications ranging from optical biomarkers to nanocarriers for cancer diagnosis and therapy. One of the major problems with using these materials therapeutically has been clinical biocompatibility. Recently, our group has developed a process to efficiently build dendritic frameworks of specific size and composition around a gold nanoparticle core by single coupling reaction. With covalently attached biocompatible dendron shells, our method should confer superior biocompatibility over some of the current coating technologies used with gold nanoparticles. First, they should resist aggregation better in biological fluids than the more conventional ligand-capped gold nanoparticles. Second, the ability to link tracking fluorophores within the open framework of these dendritic coverings rather than on the surface of the coating should lower their cellular toxicity. The development of biocompatible fluorescently labeled gold nanoparticles having conjugated antibodies against cancer-specific surface markers may provide a mechanism to not only visualize cancerous cells but also allow cell-specific destruction of the targeted cells through non-invasive thermal therapy. The development of a simpler and safer way to detect and destroy specific pathogenic cellular phenotypes is considered to be one of the highest priority areas in the field of biotechnology and medical research. To explore the potential use and applications of these novel nanoparticles in biomedical research, we are proposing an interdisciplinary research program involving a collaborative team of faculty from three Departments at CSULB: Dr. Young Shon, (Department of Chemistry) will synthesize biocompatible gold nanoparticle-cored dendrimers (NCDs), Dr Yohannes Abate, (Department of Physics) will characterize the structure of these NCDs using state-of-the art apertureless near-field scanning optical microscopy while Dr Houng-Wei Tsai, (Department of Biological Sciences) will help evaluating their potential to both optically mark as well as thermally destroy cultured cancerous cells in vitro. Dr. Tsi and Dr. Abate agreed to participate in the proposed research projects as collaborators. The work involves five major tasks: 1) Synthesis of gold NCDs with various core sizes and biocompatible dendrons. 2) Incorporation of fluorophore and linkage of targeting groups against cancer-specific surface markers to gold NCDs. 3) Characterization of functionalized NCDs using near-field scanning optical microscopy. 4) Evaluation of cytotoxicity, cell recognition, and distribution of NCDs in cultured tumor cells. 5) Hyperthermia treatments in tumor cells. This project will foster the development of a multidisciplinary research team involving scientist from three separate Departments (Chemistry, Biology, and Physics). This research plan will allow inter-laboratory technology transfer and help the PI and collaborators to develop the basic and translational research skills to become independent investigators in multi-purpose composite nanostructure research, optical microscopy materials characterization, and cancer detection and therapy. Simultaneously, this program will provide graduate and undergraduate students with unique and exciting research opportunities in nanotechnology. Through enrollment in existing research-based classes, students will be offered the opportunity to be participants in a multidisciplinary team that will collaborate on all aspects of this project - from inception, starting with basic nanoparticulate material synthesis - to completion, with the ultimate evaluation of the biomedical performance of these materials. Students will acquire hands-on experience and technical laboratory skills needed to conduct basic research regarding the synthesis, characterization and biological evaluation of novel nanostructured materials for the therapeutic treatment of diseases. They will also develop the intellectual capacity to critically analyze existing information as well as develop proficiency in the analysis, interpretation and presentation of complex data sets.

描述(申请人提供)：合成与荧光团和抗体相连的以金纳米颗粒为核心的树枝状聚合物：用于癌症治疗的智能生物标记物项目摘要在过去十年中，金纳米颗粒材料被越来越多地用于从光学生物标记物到用于癌症诊断和治疗的纳米载体的各种生物和医疗应用。在治疗上使用这些材料的主要问题之一是临床生物相容性。最近，我们团队开发了一种方法，通过单次偶联反应在金纳米颗粒核心周围高效地构建特定尺寸和组成的树枝状骨架。通过共价连接的树枝状贝壳，我们的方法应该比目前使用的一些金纳米粒子涂层技术具有更好的生物兼容性。首先，它们在生物体液中应该比更传统的带有配体的金纳米颗粒更好地抵抗聚集。其次，能够在这些树枝状覆盖物的开放框架内而不是在涂层表面连接跟踪荧光团的能力应该会降低它们的细胞毒性。具有抗癌特异性表面标记抗体的生物相容的荧光标记的金纳米颗粒的发展可能提供一种机制，不仅可以使癌细胞可视化，而且可以通过非侵入性热疗对靶细胞进行细胞特异性破坏。开发一种更简单、更安全的方法来检测和销毁特定的致病细胞表型被认为是生物技术和医学研究领域的最优先领域之一。为了探索这些新型纳米粒子在生物医学研究中的潜在用途和应用，我们正在提议一个跨学科的研究计划，由CSULB三个系的教员组成：化学系的Young Shon博士将合成生物相容的金纳米颗粒核的树状大分子(NCDs)，物理系的Yohannes Abate博士将使用最先进的无孔近场扫描光学显微镜表征这些NCDs的结构，而生物科学系的Houng-wei Tsai博士将帮助评估它们在体外光学标记和热摧毁体外培养的癌细胞的潜力。谢霆锋博士和阿巴特博士同意以合作者的身份参与拟议的研究项目。这项工作涉及五个主要任务：1)合成具有不同核尺寸和生物相容性的金NCDs。2)掺入荧光团并将抗癌特异性表面标志物的靶向基团连接到金NCDs。3)用近场扫描光学显微镜表征功能化的NCDs。4)NCDs的细胞毒性、细胞识别和在培养的肿瘤细胞中的分布。5)肿瘤细胞的热疗。该项目将促进一个多学科研究团队的发展，其中包括来自三个不同系(化学、生物和物理)的科学家。这项研究计划将允许实验室间的技术转移，并帮助PI和合作者发展基本和翻译研究技能，成为多用途复合纳米结构研究、光学显微镜材料表征以及癌症检测和治疗的独立研究人员。同时，该项目将为研究生和本科生提供独特的、令人兴奋的纳米技术研究机会。通过注册现有的以研究为基础的课程，学生将有机会成为一个多学科团队的参与者，该团队将在这个项目的各个方面进行合作-从开始，从基本的纳米颗粒材料合成-到完成，最终评估这些材料的生物医学性能。学生将获得所需的实践经验和技术实验室技能，以进行有关用于疾病治疗的新型纳米结构材料的合成、表征和生物学评估的基础研究。他们还将培养批判性分析现有信息的智力能力，以及熟练地分析、解释和介绍复杂的数据集。