Targeted MRI with Protein Cage Architectures (RMI)

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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.