Near-Infrared Fluorescence Nanoparticles for Imaging

描述(由申请人提供)： 基于近红外荧光(NIRF)的人类癌症光学成像与标准成像技术相比具有以下几个优点：极其敏感、廉价和健壮；不涉及有害辐射；并且允许实时可视化。经过验证的NIRF成像探针的开发可能会使这种新的模式成为临床上可行的分子成像方法。纳米技术的最新进展可能会大大加快新的NIRF显像剂的发现，这些显像剂不仅可以提供更高的信号强度，而且可以靶向或“报告”肿瘤特异性生物标记物的存在和生物学活性。在这项应用中，癌症研究和患者护理领域的领先机构德州大学安德森癌症中心和光学染料和纳米颗粒制造的世界领先企业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颗粒。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特性，并设计和开发使用靶向、酶激活或两者结合的纳米颗粒，以显著提高癌症检测的敏感性和特异性。我们的具体目标是1)合成和表征适合NIRF成像的聚合物壳二氧化硅纳米颗粒和交联型聚乙二醇纳米颗粒；2)确定颗粒特性对NIRF纳米颗粒药代动力学、生物分布、清除、外渗和肿瘤内分布的影响；3)确定NIRF纳米颗粒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)构建靶向血管新生血管和肿瘤细胞相关表面受体的NIRF纳米颗粒；以及5)开发智能、可激活的NIRF纳米颗粒，并在单个纳米关节系统中结合归巢配体和分子信标设计。通过结合使用核和光学成像、放射自显影和荧光显微镜，我们希望对NIRF纳米颗粒的药理学特性提供详细的见解，最终目标是获得用于人类癌症分子光学成像的有效和实用的纳米颗粒。

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.