Nanoparticle biointerfacing by platelet membrane cloaking.
Nanoparticle biointerfacing by platelet membrane cloaking.
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DOI：
10.1038/nature15373
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发表时间：
2015-10-01
期刊：
影响因子：
64.8
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Hu CM;Fang RH;Wang KC;Luk BT;Thamphiwatana S;Dehaini D;Nguyen P;Angsantikul P;Wen CH;Kroll AV;Carpenter C;Ramesh M;Qu V;Patel SH;Zhu J;Shi W;Hofman FM;Chen TC;Gao W;Zhang K;Chien S;Zhang L
功能性纳米颗粒的开发可能会受到意料之外的材料特性和生物事件的阻碍，这可能会对复杂的生理相关系统中的纳米颗粒有效性产生负面影响。尽管自下而上的纳米工程和表面化学的进步，还原功能化方法仍然不足以复制自然界中存在的复杂界面，并且无法避免暴露异物。在这里，我们报告的人血小板，这是一个独特的人口的细胞片段，坚持各种疾病相关的基板的质膜封闭的聚合物纳米粒子的制备。所得纳米颗粒具有右侧外单层膜涂层功能化的免疫调节和粘附抗原与血小板。与未涂覆的颗粒相比，血小板膜覆盖的纳米颗粒具有减少的巨噬细胞样细胞的细胞摄取，并且在自体人血浆中不存在颗粒诱导的补体活化。隐形纳米颗粒还显示出血小板模拟特性，例如选择性粘附于受损的人类和啮齿动物血管，以及增强与血小板粘附病原体的结合。在冠状动脉再狭窄的实验性大鼠模型和全身性细菌感染的小鼠模型中，多西他赛和万古霉素分别在通过血小板模拟纳米颗粒递送时显示出增强的治疗功效。由血小板膜遮盖方法实现的多方面生物界面提供了开发用于疾病靶向递送的功能性纳米颗粒的新方法。
Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can negatively impact nanoparticle effectiveness in complex, physiologically relevant systems. 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 substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. As compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and are absent of 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.