Collaborative Research: Echogenic Lipid Nanoparticles for Cocurrent Ultrasound 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：特拉华大学标题：合作研究：用于同步超声成像和药物输送的回声脂质纳米颗粒智力优势：本提案的目标是开发和研究将被识别并附着在特定酶上的回声脂质体。附着的脂质体将作为造影剂，用于酶表达程度的超声检测。酶会使脂质体失稳，释放被包裹的药物和酶的抑制剂，抑制剂的释放会自我调节药物的释放。研究的目的是优化超声造影剂和药物释放。具体来说，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裂解位点的脂肽偶联物，(2)制备含有合成的脂肽的回声脂质体，并研究明胶酶对脂质体包裹内容物的释放，(3)研究回声脂质体的稳定性和增强对比度的特性。(4)研究在没有和存在超声脉冲的情况下，明胶酶释放脂质体封装抑制剂，以及由此产生的对酶的抑制。更广泛的影响：拟议的方法，在充分开发后，将在诊断和靶向给药领域得到应用。在不久的将来，酶触发脂质体释放的领域具有巨大的增长潜力。这项研究将发起一项多大学跨学科的倡议，学生将在化学、生物学和工程学结合在一起的环境中接受训练，以解决一个重要问题。这两所学院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养本科生和研究生。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（一个HBCU）的合作伙伴建立了联系，以确定有才华的本科生研究实习生，并为他们在特拉华大学的研究生学习提供培训。

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.