Collaborative Research: Echogenic Lipid Nanoparticles for Cocurrent Ultrasound Imaging and Drug Delivery

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ID: MPS/DMR/BMAT(7623) 1005011 PI: Mallik, Sanku ORG: North Dakota State UniversityID: MPS/DMR/BMAT(7623) 1005238 PI: Sarkar, Kausik ORG: University of DelawareTitle: Collaborative Research: Echogenic Lipid Nanoparticles for Concurrent Ultrasound Imaging and Drug DeliveryINTELLECTUAL MERIT: The goal of this proposal is to develop and investigate echogenic liposomes that will be recognized by and attach to a specific enzyme. The attached liposomes will act as contrast agents for ultrasound assay of the extent of expression of the enzyme. The enzyme will destabilize the liposome releasing encapsulated drugs as well as inhibitors for the enzyme, and the release of inhibitors will self-regulate the drug release. The investigation is directed towards optimizing ultrasound contrast and drug release. Specifically, the objectives of this proposal are to: (1) synthesize lipid-peptide conjugates containing the cleavage site for gelatinase enzymes that are over expressed in atherosclerotic plaque, (2) prepare echogenic liposomes incorporating the synthesized lipopeptides and investigate the release of liposome-encapsulated contents by gelatinases, (3) investigate stability and contrast enhancing properties of echogenic liposomes, and (4) investigate the release of liposome-encapsulated inhibitors by gelatinases in the absence and presence of ultrasonic pulses and the resultant inhibition of the enzyme.BROADER IMPACTS: The proposed methodology, when fully developed, will find applications in the areas of diagnostics and targeted drug delivery. The area of the enzyme-triggered content release from liposomes has enormous potential to grow in the near future. The research will initiate a multi-university cross-disciplinary initiative where students will be trained in an environment where chemistry, biology and engineering will be brought together to solve an important problem. Both PIs are dedicated to teaching and training the next generation of scientists and engineers. The project will involve training undergraduate and graduate students in a cross-disciplinary environment. The proposed research will involve two Native American undergraduate students in the Mallik lab at North Dakota State. Sarkar has established a link with a collaborator in Morgan State University (an HBCU) to identify talented undergraduate research interns and to groom them for graduate study at the University of Delaware.