This application aims to establish the Center for Translational Cardiovascular Nanomedicine, a highly collaborative and multidisciplinary Program of Excellence in Nanotechnology (PEN). The broad and long-term vision of this PEN is to develop and apply nanotechnology and biomolecular engineering tools and approaches to address compelling medical needs in the detection and treatment of atherosclerosis and the repair of damaged vasculature and heart tissue. Cardiovascular disease remains the leading cause of death in the US, and there is an un-met need to inform the state and activity of atherosclerotic plaques, to deliver therapeutics directly to lesions, and to guide the evaluation of therapy. Nanotechnology has the potential to address these challenges. We will develop and apply: (1) nanoparticle based PET and dual-modality PET/MR contrast agents for in vivo imaging of atherosclerotic plaques, (2) fluorescence imaging probes and gold-nanoparticle sensors for in vitro detection of atherosclerosis, (3) nanocarriers for targeted delivery of siRNA and drug molecules to lesions in vivo, and (4) nanotools in stem cell research for personalized repair of damaged tissue. Our specific milestones include the ability to deliver 20% injected dose/gram in diseased tissue, achieve RNA knockdown exceeding 70% in primary cell lines and generate patient-specific endothelial cells and cardiomyocytes with a 10-fold increase in long-term viability. The goals of this PEN are to establish the nano-toolbox and nano-cardiology knowledge-base, to translate the nano-scale tools and technologies to clinical applications in the detection and treatment of cardiovascular disease and to train the next generation of leaders in cardiovascular nanomedicine.
