Collaborative Research: Echogenic Lipid Nanoparticle for Concurrent Untrasound Imaging and Drug Delivery

ID：MPS/DMR/BMAT（7623）1005011 PI：Mallik、Sanku ORG：北达科他州State UniversityID：MPS/DMR/BMAT（7623）1005238 PI：Sarkar，Kausik ORG：特拉华大学标题：合作研究：用于同步超声成像和药物递送的回声脂质纳米颗粒智力优势：该提案的目标是开发和研究将被识别并附着于特定酶的回声脂质体。 附着的脂质体将作为用于酶表达程度的超声测定的造影剂。 酶将使脂质体不稳定，从而释放包封的药物以及酶的抑制剂，并且抑制剂的释放将自调节药物释放。 该研究旨在优化超声对比度和药物释放。 具体而言，本提案的目标是：（1）合成含有在动脉粥样硬化斑块中过表达的明胶酶的切割位点的脂质-肽缀合物，（2）制备掺入合成的脂肽的回声脂质体，并研究明胶酶对脂质体包封的内容物的释放，（3）研究回声脂质体的稳定性和对比增强性质，和（4）研究明胶酶在超声脉冲的存在和不存在下释放脂质体包裹的抑制剂以及由此产生的酶抑制。更广泛的影响：所提出的方法，当充分发展，将发现在诊断和靶向药物输送领域的应用。 在不久的将来，酶触发脂质体内容物释放的领域具有巨大的增长潜力。 该研究将启动一项多大学跨学科计划，学生将在化学，生物学和工程学的环境中接受培训，以解决一个重要问题。 这两个PI都致力于教育和培训下一代科学家和工程师。该项目将涉及在跨学科环境中培训本科生和研究生。 这项拟议中的研究将涉及北达科他州Mallik实验室的两名美国原住民本科生。 Sarkar已经与摩根州立大学（HBCU）的合作者建立了联系，以确定有才华的本科研究实习生，并培养他们在特拉华州大学的研究生学习。

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.