Our collaborative group has a common goal of developing the next generation of diagnostic, therapeutic, and “theranostic” agents for cardiovascular disease. We present here a comprehensive and integrated program of goal-oriented research, designed to maximally leverage the unique contributions of this trans-Pacific collaboration. The Thaxton Lab has pioneered the synthesis and characterization of biomimetic high density lipoprotein nanoparticles (HDL NPs) which have geometry, surface chemistry, and biologic activity of natural HDL. Dr. Mutharasan has further adapted the HDL NP concept to develop diagnostic sensors for clinical use in atherosclerosis. The Venkatraman Lab has developed liposomal structures encapsulated with therapeutic or biomolecular cargo, as well as techniques to localize and control the delivery of bioactive agents. The Dravid Lab has developed strategies for encapsulating magnetic nanostructures (MNS) in biocompatible nanoconstructs including HDL NPs, liposomes and hydrogels which enables the monitoring of the fate of imaging agents starting from synthesis to their physiological pathway, using advanced electron and magnetic resonance (MR)-based techniques. Here we propose using this combined expertise to lead a three-front early stage assault on cardiovascular disease that enables precise risk-assessment, anatomic detection, and early treatment of vulnerable to rupture atherosclerotic lesions. From the diagnostic perspective we propose to: 1) Develop clinically ready ex vivo physiologic assays using the HDL NP platform, and 2) Create novel in vivo diagnostic agents using the MNS and liposomal platforms for non-invasive MR imaging, detection and monitoring of vulnerable atherosclerotic lesions; utilizing T1, T2 and ratio-weighted imaging protocol/s. From the therapeutic perspective, we propose using nanoscale formulations of liposomes, hydrogels and HDL NP to develop therapies, some with anti-inflammatory cargo, to prevent and treat cardiovascular disease. The proposed constructs will also enable simultaneous diagnostic MR imaging and localized therapy (i.e., theranostic administration) for cardiovascular disease. Collectively, the proposal envisages both upstream (Exploratory Nanomedicine) and downstream (Translational Nanomedicine) approaches. Extensive and appropriate animal studies are proposed to address the prospects for potential clinical translation of the proposed agents. Project success will result in critical next generation diagnostic and therapeutic agents for cardiovascular disease.
|Effective start/end date||11/1/14 → 10/31/20|
- Nanyang Technological University (Agmt 10/27/14)