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Nanoparticle biointerfacing by platelet membrane cloaking

纳米颗粒 血小板活化 化学 表面改性 生物物理学 纳米工程 人口 纳米技术 血小板 材料科学 免疫学 医学 生物化学 生物 环境卫生 物理化学
作者
Che‐Ming Jack Hu,Ronnie H. Fang,Kuei-Chun Wang,Brian T. Luk,Soracha Thamphiwatana,Diana Dehaini,Phu Hung Nguyen,Pavimol Angsantikul,Cindy Wen,Ashley V. Kroll,Cody W. Carpenter,Manikantan Ramesh,Vivian Qu,Sheila V. Patel,Jie Zhu,William Y. Shi,Florence M. Hofman,Thomas C. Chen,Weiwei Gao,Kang Zhang,Shu Chien,Liangfang Zhang
出处
期刊:Nature [Springer Nature]
卷期号:526 (7571): 118-121 被引量:1404
标识
DOI:10.1038/nature15373
摘要

The authors report a new biomimetic nanodelivery platform in which polymeric nanoparticles enclosed in the plasma membrane of human platelets are used for disease-relevant targeting, and the therapeutic potential of the concept is demonstrated in animal models of coronary restenosis and systemic bacterial infection. The properties of blood platelets — small discoid cells that carry out a broad range of functions related to haemostasis — marks them out as prime candidates to form the basis of drug delivery systems. These authors report a new nanoparticle-based delivery platform, in which polymeric nanoparticles are enclosed in the plasma membrane of human platelets. They demonstrate the use of these platelet-membrane cloaked nanoparticles for antibiotic delivery in murine models for cardiovascular disease and systemic bacterial infection. Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems1,2,3. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates4,5,6,7. 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.
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