Microfluidic Examination of the "Hard" Biomolecular Corona Formed on Engineered Particles in Different Biological Milieu.
Microfluidic Examination of the "Hard" Biomolecular Corona Formed on Engineered Particles in Different Biological Milieu.
复制标题
不同生物环境中工程颗粒上形成的“硬”生物分子电晕的微流体检查。
DOI：
10.1021/acs.biomac.8b00196
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发表时间：
2018
影响因子：
6.2
通讯作者：
F. Caruso
中科院分区：
文献类型：
--
作者：
A. Weiss;K. Kempe;S. Förster;F. Caruso
工程颗粒周围生物分子冠的形成在很大程度上决定了它们在体外和体内的生物学行为。为了从根本上了解颗粒设计和生物环境如何影响“硬”生物分子冠的形成，我们使用微流体进行了一系列体外研究。这种设置允许产生动态孵育环境，精确控制所施加的流速、流方向和通道尺寸，从而允许精确控制流体流动和施加于蛋白质和颗粒的剪切。我们使用了介孔二氧化硅颗粒，聚（2-甲基丙烯酰氧基乙基磷酰胆碱）（PMPC）涂覆的二氧化硅混合颗粒，和PMPC副本颗粒（通过去除二氧化硅颗粒模板获得），分别代表高，中，低污垢颗粒系统。实验中使用的蛋白质来源是人血清或人全血。流量，颗粒表面性质，孵育介质，和孵育时间上的生物分子电晕形成的影响进行检查。我们的数据表明，在人血液中孵育后，与人血清相比，颗粒上的蛋白质粘附增强，并且动态孵育导致更复杂的冠。通过改变从2秒到15分钟的孵育时间，我们表明，“硬”生物分子冠动力学细分为两个阶段，包括一个紧密结合的蛋白质层直接与颗粒表面和松散相关的蛋白质层相互作用。了解颗粒设计参数和生物因素对电晕组成的影响，以及其动态组装，可能有助于更准确地预测电晕的形成，因此有助于设计先进的药物递送载体。
The formation of a biomolecular corona around engineered particles determines, in large part, their biological behavior in vitro and in vivo. To gain a fundamental understanding of how particle design and the biological milieu influence the formation of the "hard" biomolecular corona, we conduct a series of in vitro studies using microfluidics. This setup allows the generation of a dynamic incubation environment with precise control over the applied flow rate, stream orientation, and channel dimensions, thus allowing accurate control of the fluid flow and the shear applied to the proteins and particles. We used mesoporous silica particles, poly(2-methacryloyloxyethylphosphorylcholine) (PMPC)-coated silica hybrid particles, and PMPC replica particles (obtained by removal of the silica particle templates), representing high-, intermediate-, and low-fouling particle systems, respectively. The protein source used in the experiments was either human serum or human full blood. The effects of flow, particle surface properties, incubation medium, and incubation time on the formation of the biomolecular corona formation are examined. Our data show that protein adhesion on particles is enhanced after incubation in human blood compared to human serum and that dynamic incubation leads to a more complex corona. By varying the incubation time from 2 s to 15 min, we demonstrate that the "hard" biomolecular corona is kinetically subdivided into two phases comprising a tightly bound layer of proteins interacting directly with the particle surface and a loosely associated protein layer. Understanding the influence of particle design parameters and biological factors on the corona composition, as well as its dynamic assembly, may facilitate more accurate prediction of corona formation and therefore assist in the design of advanced drug delivery vehicles.