Macrophage Membrane-Coated Nanoparticles for Endotoxin Neutralization

非技术：该奖项授予加州大学圣地亚哥分校，旨在探索一种极具创新性的策略，快速有效地从血液中去除内毒素，并研究这种新的解毒方法的基本原理。内毒素是脓毒症的重要致病诱因，是危及生命的并发症，造成重大的医疗负担。新出现的证据表明，有效的内毒素清除对于成功的败血症管理至关重要，然而，这仍然是一个未满足的临床需求。在这个项目中，一种基于生物材料的纳米结构，由安全聚合物和巨噬细胞膜组成，被提议作为毒素诱饵来吸收各种不同的内毒素，从而减少它们对靶细胞的影响。作为这个计划的一个组成部分，教育部分将被仔细地执行，以促进生物材料科学和工程的持续发展。将特别努力培训生物材料和纳米医学领域的新一代合作和熟练的研究人员和教育工作者。技术：该奖项的研究目标是开发和研究一种新的巨噬细胞膜包被纳米颗粒（表示MØ-NP）平台，用于内毒素中和。所采取的方法将是利用一种创新和强大的自上而下的策略，将巨噬细胞的整个细胞膜转移到合成纳米颗粒的表面。经过这种修饰的纳米颗粒有望保存表面抗原，并表现出与其源细胞相似的功能。在这个特殊的项目中，MØ-NP有望继承巨噬细胞结合内毒素的能力。为了实现主要目标，拟议项目将进行三项具体研究任务：(i)编制和描述MØ-NPs；（ii）研究MØ-NPs的内毒素结合能力；（iii）研究MØ-NPs在体外中和内毒素的作用。此外，通过该项目，PI将培养一支跨学科和多层次合作的青年研究团队，为少数民族学生提供刺激的研究经验，并加强K-12学生和整个社区的科学教育。

NON-TECHNICAL: This award to the University of California, San Diego is to explore an extremely innovative strategy for rapid and effective removal of endotoxins from the bloodstream and to investigate the fundamental principles of such a new detoxification approach. Endotoxin is an important pathogenic trigger of sepsis, a life-threatening complication imposing a significant healthcare burden. Emerging evidence suggests that effective endotoxin removal is critical for successful sepsis management, which however remains an unmet clinical need. In this project, a biomaterials-based nanostructure, consisting of safe polymers and macrophage membranes, is proposed to function as a toxin decoy to absorb a wide range of different endotoxins and thus minimize their with the target cells. As an integral part of this proposed project, the education components will be carefully carried out to contribute to the continual growth of biomaterials science and engineering. Particular efforts will be put on training a new generation of collaborative and skilled researchers and educators in the field of biomaterials and nanomedicine.TECHNICAL: The research objective of this award is to develop and investigate a novel macrophage membrane-coated nanoparticle (denoted MØ-NP) platform for endotoxin neutralization. The approach taken will be to utilize an innovative and robust top-down strategy to transfer the entire cellular membrane of macrophage cells onto the surface of synthetic nanoparticles. A nanoparticle thus modified is expected to preserve the surface antigens and exhibit similar functionalities as its source cells. In this particular project, the MØ-NP is expected to inherit the macrophage's capabilities for binding endotoxins. To achieve the primary goal, three specific research tasks will be pursued in the proposed project: (i) prepare and characterize MØ-NPs; (ii) study endotoxin-binding capabilities of MØ-NPs; and (iii) investigate endotoxin neutralization by MØ-NPs in vitro. Further, through this project the PI will train a team of interdisciplinary and multi-level collaborative young investigators, provide minority students with stimulating research experience, and enhance scientific education among K-12 students and community at large.