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

ID：MPS/dmr/bmat(7623)1005011 PI：Mallik，Sanku ORG：北达科他州立大学ID：MPS/dmr/bmat(7623)1005238 PI：Sarkar，Kausik ORG：DelawareUniversity：Collaborative Research：用于同时进行超声成像和药物递送的回声脂质纳米粒INTELLECTUAL优点：这项建议的目标是开发和研究可被特定酶识别并附着到特定酶上的回声脂质体。附着的脂质体将作为造影剂，用于超声检测酶的表达程度。该酶会破坏脂质体的稳定性，释放药物以及酶的抑制剂，而抑制剂的释放将自我调节药物的释放。这项研究旨在优化超声造影剂和药物释放。具体地说，这项建议的目标是：(1)合成含有在动脉粥样硬化斑块中过度表达的明胶酶酶的裂解位点的脂肽结合物，(2)制备含有合成脂肽的回声脂质体，并研究明胶酶释放脂质体包裹的内容物，(3)研究回声脂质体的稳定性和增强对比度的性能，以及(4)研究明胶酶在没有和存在超声脉冲的情况下释放脂质体包埋的抑制剂以及由此产生的酶的抑制作用。在不久的将来，酶引发的脂质体释放的内容物领域具有巨大的增长潜力。这项研究将发起一项跨大学的跨学科倡议，学生将在一个将化学、生物和工程结合在一起解决一个重要问题的环境中接受培训。这两家私人投资机构都致力于教授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。这项拟议的研究将涉及北达科他州马利克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)的一位合作者建立了联系，以寻找有才华的本科生研究型实习生，并为他们在特拉华大学的研究生学习进行培训。

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.