Targeted MRI with Protein Cage Architectures (RMI)

描述(由申请人提供)：我们的总体目标是创造和测试新一代细胞靶向的磁共振造影剂。其目的将是在医学上广泛应用的体外和体内检测和成像分子水平事件的能力方面至少实现数量级的提高。这项建议是一项多学科的努力，结合了心血管、血管生物学、核磁共振、病毒学、合成无机和纳米材料化学方面的成熟专业知识。整个方法将结合使用非传染性病毒和其他蛋白质笼结构，用于细胞特异性靶向配体的多价展示，高性能金属成像试剂，用于使用MRI进行功能和细胞成像。这种方法的优点是由于病毒结构的大小以及高密度呈现靶向配体和自由接触水的金属结合位点，大大增加了旋转关联时间。这项建议的具体目标是：(1)合成高密度呈现细胞靶向配体和高磁矩材料的蛋白质笼结构，(Ii)控制制备含有功能化细胞靶向配体和磁共振造影剂的蛋白质笼纳米颗粒簇，以及(Hi)体外和体内磁共振评价功能化蛋白质笼结构，包括用于检测纳米颗粒造影剂的改进的磁共振技术。使用最先进的设备创建和评估这些材料作为功能性磁共振造影剂，将为迭代过程提供快速和直接的反馈，以创造下一代高性能功能性磁共振造影剂。

DESCRIPTION (provided by applicant): Our overall goal is to create and test a new generation of cell- targeted MRI contrast agents. The aim will be to achieve at least an order of magnitude increase in improvement in the ability to detect and image molecular level events in vitro and in vivo with broad applications in medicine. This proposal is a multidisciplinary effort, combining established expertise in cardiovascular, vascular biology, MRI, virology, synthetic inorganic and nano-materials chemistry. The overall approach will combine the use of non-infectious virus and other protein cage architectures for multivalent display of cell-specific targeting ligands, high performance metal based imaging agents, for functional and cellular imaging using MRI. The advantage of this approach is a substantial increase in rotational correlation time due to the size of the virus architecture in combination with high-density presentation of targeting ligands and metal binding sites with free access to water. The specific objectives of this proposal are (1) synthesis of protein cage architectures with high-density presentation of both cell targeting ligands and high magnetic moment materials, (ii) controlled fabrication of protein cage nano-particle clusters incorporating functionalized cell targeting ligands and MRI contrast agents, and (Hi) in vitro and in vivo MRI evaluation of functionalized protein cage architectures including improved MRI techniques for detecting nano-particle contrast agents. Creation and evaluation of these materials as functional MR contrast agents using state-of the-art facilities will provide rapid and direct feedback for an iterative process to create the next generation of high performance functional MRI contrast agents.