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Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. We have developed a procedure to enclose polymeric nanoparticles in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures, as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.

 

Shu Chien is the founding chair of the Department of Bioengineering at UC San Diego. In 2008, Dr. Chien became the founding Director of UC San Diego’s Institute of Engineering in Medicine to foster collaborations among the faculty of UCSD and with research institutes and biomedical companies in San Diego. Dr. Chien’s studies are leading to a new understanding about the pathophysiological mechanisms of atherosclerosis and hypertension, and to the development of therapeutical approaches for cardiovascular disease.