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: 8152293
• 负责人: Young Shon
• 金额: $ 9.81万
• 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/8152293
• 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; Fever; Fostering; Funding; Goals; Gold; Heating; Human; 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; hyperthermia treatment; interest; killings; macromolecule; meetings; multidisciplinary; nanocarrier; nanomaterials; nanoparticle; nanoparticulate; nanoscience; nanostructured; neoplastic cell; novel; programs; skills; surface coating; tumor

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. PUBLIC HEALTH RELEVANCE: The advances in nanoscience and nanotechnology greatly promote the rapid development of various new systems for cancer therapy in current medicine. An ideal nanoparticle platform should be endowed with targeting, imaging, and therapeutic functionalities, which allow for targeting, imaging, and killing of cancer cells. Nanoparticle-cored dendrimers (NCDs) are a new class of highly branched, synthetic macromolecules with a nanoparticle core and well-defined dendritic wedges. The unique structural properties of NCDs make them ideal candidates for use as a multifunctional platform for the diagnostic and treatment of cancer. The markers for the proposed study are gold NCDs, which are linked with fluorophores and cancer-specific antibodies. This proposal is particularly designed to prove the feasibility of using this novel, multifunctional composite nanomaterial as a fluorescence image enhancer and hyperthermia guide. Due to its capability of accurately focusing energy to the targeted areas (the site of the tumor), hyperthermia has been attracting much interest. The most important advantage of using hyperthermia is its few side effects, unlike the chemotherapy used for the current cancer treatment.

描述（由申请人提供）：与荧光团和抗体连接的金纳米颗粒核心树枝状聚合物的合成：用于癌症治疗的智能生物标记物项目摘要在​​过去的十年中，金纳米颗粒材料已越来越多地用于各种生物和医学应用，从光学生物标记物到用于癌症诊断和治疗的纳米载体。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，我们的团队开发了一种通过单次偶联反应在金纳米粒子核心周围有效构建特定尺寸和成分的树突状框架的方法。通过共价连接的生物相容性树枝状大分子壳，我们的方法应该比目前使用金纳米颗粒的一些涂层技术具有更好的生物相容性。首先，它们应该比更传统的配体封端的金纳米粒子更好地抵抗生物体液中的聚集。其次，在这些树枝状覆盖物的开放框架内而不是在涂层表面上连接追踪荧光团的能力应该会降低它们的细胞毒性。具有针对癌症特异性表面标记物的缀合抗体的生物相容性荧光标记金纳米颗粒的开发可能提供一种机制，不仅可以使癌细胞可视化，而且还可以通过非侵入性热疗法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破坏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颗粒在生物医学研究中的潜在用途和应用，我们提出了一项跨学科研究计划，该计划涉及来自 CSULB 三个系的教师合作团队：Young Shon 博士（化学系）将合成生物相容性金纳米颗粒 - Yohannes Abate 博士（物理系）将使用最先进的无孔径近场扫描光学显微镜来表征这些 NCD 的结构，同时 Dr. Houng-Wei Tsai（生物科学系）将帮助评估它们在体外光学标记和热破坏培养的癌细胞方面的潜力。 Tsi 博士和 Abate 博士同意作为合作者参与拟议的研究项目。 这项工作涉及五个主要任务：1）合成具有不同核心尺寸和生物相容性树枝的金NCD。 2) 荧光团的掺入以及针对癌症特异性表面标记物的靶向基团与金非传染性疾病的连接。 3) 使用近场扫描光学显微镜表征功能化 NCD。 4) 评估培养肿瘤细胞中NCD的细胞毒性、细胞识别和分布。 5）肿瘤细胞的热疗。 该项目将促进多学科研究团队的发展，该团队由来自三个不同部门（化学、生物学和物理）的科学家组成。该研究计划将允许实验室间技术转让，并帮助 PI 和合作者发展基础和转化研究技能，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方面的独立研究人员。同时，该计划将为研究生和本科生提供纳米技术方面独特且令人兴奋的研究机会。通过注册现有的研究型课程，学生将有机会成为多学科团队的参与者，该团队将在该项目的各个方面进行合作 - 从开始，从基本纳米颗粒材料合成开始 - 到完成，最终评估这些材料的生物医学性能。学生将获得进行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所需的实践经验和技术实验室技能。他们还将培养批判性分析现有信息的智力能力，以及提高分析、解释和呈现复杂数据集的能力。 公共健康相关性：纳米科学和纳米技术的进步极大地促进了当前医学中各种癌症治疗新系统的快速发展。理想的纳米颗粒平台应具有靶向、成像和治疗功能，从而能够靶向、成像和杀死癌细胞。纳米颗粒核心树枝状聚合物 (NCD) 是一类新型高度支化的合成大分子，具有纳米颗粒核心和明确的树状楔形结构。非传染性疾病的独特结构特性使其成为癌症诊断和治疗的多功能平台的理想候选者。拟议研究的标记物是金质非传染性疾病，它与荧光团和癌症特异性抗体相关。 该提案专门旨在证明使用这种新型多功能复合纳米材料作为荧光图像增强剂和热疗引导剂的可行性。由于热疗能够将能量精确地聚焦到目标区域（肿瘤部位），因此引起了人们的广泛关注。与当前癌症治疗中使用的化疗不同，热疗最重要的优点是副作用很少。