Near-Infrared Fluorescence Nanoparticles for Imaging

用于成像的近红外荧光纳米颗粒

• 批准号: 7051352
• 负责人: CHUN LI
• 金额: $ 64.1万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7051352
• 关键词: Kaposi' s sarcoma; angiogenesis; athymic mouse; autoradiography; bioimaging /biomedical imaging; biomarker; cell line; chemical synthesis; contrast media; crosslink; cytotoxicity; diagnosis design /evaluation; early diagnosis; enzyme activity; fluorescence microscopy; infrared spectrometry; integrins; melanoma; molecular /cellular imaging; nanotechnology; neoplasm /cancer blood supply; neoplasm /cancer radiodiagnosis; optics; particle; pharmacokinetics; polyethylene glycols; polymers; xenotransplantation

DESCRIPTION (provided by applicant): Near-infrared fluorescence (NIRF)-based optical imaging of human cancers has several advantages over standard imaging techniques in that it is extremely sensitive, inexpensive, and robust; involves no harmful radiation; and allows real-time visualization. The development of well-validated NIRF imaging probes may lead to this new modality becoming clinically viable for molecular imaging. Recent advances in nanotechnology are likely to substantially accelerate the discovery of new NIRF imaging agents that can not only provide increased signal intensity, but also target or "report" both the presence and the biologic activity of tumor-specific biomarkers. In this application, U. T. M. D Anderson Cancer Center, a leading institution in cancer research and patient care, and Eastman Kodak Co., a world leader in the fabrication of optical dyes and nanoparticles, will team to develop novel nanoparticles for molecular optical imaging applications. Our goals are to systematically investigate the in vivo pharmacologic properties of nanoparticles derived from Kodak's platform technology, and to design and develop nanoparticles that use targeting, enzyme activation, or a combination of both features to achieve significant improvements in the sensitivity and specificity of cancer detection. Our specific aims are 1) to synthesize and characterize polymer-shelled silica nanoparticles and cross-linked PEG nanoparticles suitable for NIRF imaging; 2) to establish the effect of particle characteristics on the pharmacokinetics, biodistribution, clearance, extravasation, and intratumoral distribution of NIRF nanoparticles; 3) to establish the stability and signal intensity of NIRF nanoparticles in vivo and the specificity of their retention in tumors; 4) to construct NIRF nanoparticles targeted to angiogenic blood vessels and to tumor cell-associated surface receptors; and 5) to develop smart, activatable NIRF nanoparticles and to combine homing ligand and molecular beacon designs in a single nanoparticulate system. By using a combination of nuclear and optical imaging, autoradiography, and fluorescence microscopy, we expect to provide detailed insights into the pharmacologic properties of NIRF nanoparticles, with the ultimate goal of obtaining nanoparticles that are effective and practical for molecular optical imaging of human cancers.

描述（由申请人提供）： 近红外荧光（NIRF）的人类癌症的光学成像比标准成像技术具有多个优点，因为它非常敏感，廉价且健壮。不涉及有害辐射；并允许实时可视化。经过验证的NIRF成像探针的开发可能会导致这种新的模式对于分子成像在临床上可行。 纳米技术的最新进展可能会大大加速新的NIRF成像剂，这些新NIRF成像剂不仅可以提供增加的信号强度，还可以靶向或“报告”肿瘤特异性生物标志物的存在和生物学活性。在此应用程序中，癌症研究和患者护理领域的领先机构U. T. M. D Anderson癌症中心以及伊斯曼柯达公司（Eastman Kodak Co.我们的目标是系统地研究源自柯达平台技术的纳米颗粒的体内药理学特性，并设计和开发使用靶向，酶激活或两种功能的纳米颗粒来实现癌症检测的敏感性和特异性的重大提高。我们的具体目的是1）合成和表征聚合物壳的二氧化硅纳米颗粒和适合NIRF成像的交联的PEG纳米颗粒； 2）建立颗粒特征对药代动力学的影响，生物分布，清除，渗出和NIRF纳米颗粒的肿瘤内分布； 3）在体内建立NIRF纳米颗粒的稳定性和信号强度及其在肿瘤中保留的特异性； 4）构建针对血管生成血管和肿瘤细胞相关表面受体的NIRF纳米颗粒； 5）开发智能的，可激活的NIRF纳米颗粒，并将归巢配体和分子信标组合在单个纳米标志系统中。通过结合核成像，自显影和荧光显微镜的结合，我们希望对NIRF纳米颗粒的药理特性提供详细的见解，并最终的目的是获得有效且实用的人类癌分子光学成像的纳米颗粒。