Near-Infrared Fluorescence Nanoparticles for Imaging

描述（由申请人提供）： 与标准成像技术相比，基于近红外荧光 (NIRF) 的人类癌症光学成像具有多个优点，因为它极其灵敏、廉价且稳定。不涉及有害辐射；并允许实时可视化。经过充分验证的 NIRF 成像探针的开发可能会导致这种新的分子成像模式在临床上变得可行。 纳米技术的最新进展可能会大大加速新型 NIRF 成像剂的发现，这些成像剂不仅可以提供增强的信号强度，还可以靶向或“报告”肿瘤特异性生物标志物的存在和生物活性。在这项应用中，癌症研究和患者护理领域的领先机构 U.T.M.D. 安德森癌症中心和光学染料和纳米粒子制造领域的世界领先者伊士曼柯达公司将合作开发用于分子光学成像应用的新型纳米粒子。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，并设计和开发利用靶向、酶激活或两者功能组合的纳米颗粒，以显着提高癌症检测的灵敏度和特异性。我们的具体目标是 1) 合成和表征适用于 NIRF 成像的聚合物壳二氧化硅纳米颗粒和交联 PEG 纳米颗粒； 2) 确定颗粒特性对 NIRF 纳米颗粒药代动力学、生物分布、清除、外渗和瘤内分布的影响； 3）确定NIRF纳米粒子在体内的稳定性和信号强度以及它们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、可激活的 NIRF 纳米粒子，并将寻靶配体和分子信标设计结​​合在单个纳米粒子系统中。通过结合核成像和光学成像、放射自显影和荧光显微镜，我们期望对 NIRF 纳米颗粒的药理特性提供详细的了解，最终目标是获得对人类癌症分子光学成像有效且实用的纳米颗粒。

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.