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.
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.
