Targeted MRI with Protein Cage Architectures (RMI)

描述（由申请人提供）：我们的总体目标是创建和测试新一代细胞靶向MRI造影剂。其目的将是实现在体外和体内检测和成像分子水平事件的能力方面的至少一个数量级的提高，在医学中具有广泛的应用。该提案是一项多学科的努力，结合了心血管，血管生物学，MRI，病毒学，合成无机和纳米材料化学方面的专业知识。整个方法将联合收割机结合使用非感染性病毒和其他蛋白笼结构，用于多价展示细胞特异性靶向配体、高性能金属基成像剂，用于使用MRI的功能和细胞成像。这种方法的优点是旋转相关时间的大幅增加，这是由于病毒结构的大小与靶向配体和金属结合位点的高密度呈现以及自由接近水的组合。该提案的具体目标是（1）合成具有细胞靶向配体和高磁矩材料两者的高密度呈现的蛋白质笼结构，（ii）结合有功能化细胞靶向配体和MRI造影剂的蛋白质笼纳米颗粒簇的受控制造，和（iii）功能化蛋白笼结构的体外和体内MRI评价，包括用于检测纳米颗粒造影剂的改进的MRI技术。 使用最先进的设施创建和评价这些材料作为功能性MR造影剂，将为迭代过程提供快速和直接的反馈，以创建下一代高性能功能性MRI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.