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）：与荧光团和抗体相关的金纳米颗粒的树枝状聚合物的合成：癌症治疗项目的智能生物标志物在过去十年内摘要，在过去十年中，金纳米构造材料越来越多地用于用于多样化的生物学和医疗应用，从光学生物标志物到纳米型癌症和癌症诊断。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，我们的小组开发了一个过程，通过单个耦合反应有效地围绕金纳米粒子核心建立了特定大小和组成的树突框架。使用共同附着的生物相容性树枝状壳，我们的方法应赋予与金纳米颗粒一起使用的一些当前涂料技术相比。首先，它们在生物流体中应更好地抵抗聚集，而不是传统的配体封型金纳米颗粒。其次，在这些树突覆盖物的开放框架内而不是在涂层表面上连接跟踪荧光团的能力应降低其细胞毒性。具有与癌症特异性表面标记的抗体相结合的抗体的生物相容性荧光标记的金纳米颗粒的发展可能不仅可以使癌细胞可视化，还可以通过非侵入性热治疗对靶向细胞进行特异性破坏。一种更简单，更安全的方法来检测和破坏特定的致病性细胞表型被认为是生物技术和医学研究领域最高的优先领域之一。 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 NCD使用最先进的无视野扫描光学显微镜，而Houng-wei Tsai（生物科学系）将有助于评估其在体外的光学标记和热破坏培养的癌细胞的潜力。 TSI博士和Abate博士同意作为合作者参加拟议的研究项目。 这项工作涉及五个主要任务：1）与具有各种核心大小和生物相容性树突的金NCD合成。 2）将荧光团和针对癌症特异性表面标志物与金NCD的靶向组连接在一起。 3）使用近场扫描光学显微镜对功能化的NCD进行表征。 4）评估NCD在培养的肿瘤细胞中的细胞毒性，细胞识别和分布。 5）肿瘤细胞中的高温治疗。 该项目将促进涉及来自三个独立部门（化学，生物学和物理学）的科学家的多学科研究团队的发展。该研究计划将允许实验室间的技术转移，并帮助PI和合作者开发基本和转化的研究技能，成为多功能复合纳米结构研究，光学显微镜材料表征以及癌症检测和治疗的独立研究者。同时，该计划将为研究生和本科生提供纳米技术方面的独特而激动人心的研究机会。通过入学现有基于研究的课程，将为学生提供机会成为一个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 - 从建立开始，从基本的纳米纳米构成材料综合开始，一直到完成，并对这些材料的生物医学表现进行最终评估。学生将获得有关对疾病治疗的新型纳米结构材料的合成，表征和生物学评估进行基础研究所需的动手经验和技术实验室技能。他们还将发展智力能力，以批判性地分析现有信息，并发展熟练度，以分析复杂数据集的分析，解释和呈现。 公共卫生相关性：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新的癌症治疗系统的快速发展。理想的纳米颗粒平台应赋予靶向，成像和治疗功能，从而允许靶向，成像和杀死癌细胞。纳米颗粒甲级生物发生器（NCDS）是一类新的高度分支，合成的大分子，具有纳米颗粒核心和定义明确的树突状楔。 NCD的独特结构特性使其成为用于诊断和治疗癌症的多功能平台的理想候选者。拟议研究的标记是金NCD，它们与荧光团和癌症特异性抗体有关。 该建议尤其旨在证明使用这种新型的多功能复合纳米材料作为荧光图像增强子和高温指南的可行性。由于其能够将能量准确集中到靶向区域（肿瘤部位）的能力，因此热疗引起了很多兴趣。使用高温的最重要优点是它的副作用几乎与用于当前癌症治疗的化学疗法不同。