Powder Technology Laboratory, Institute of Materials, Ecole polytechnique fédérale de Lausanne, EPFL STI IMX LTP, Station 12, 1015, Lausanne, Switzerland.
Department of Chemistry and Biochemistry, University of Bern, N431, Freiestrasse 3, 3012, Bern, Switzerland.
Small. 2017 Aug;13(29). doi: 10.1002/smll.201700409. Epub 2017 Jun 5.
In biological environments, the surface of nanoparticles (NPs) are modified by protein corona (PC) that determines their biological behavior. Unfortunately, in vitro tests still give different PC than in vivo tests causing in vitro-in vivo discrepancy; hence, in vitro studies are not indicative for the NPs' behavior in vivo. Here is demonstrated that PC in vitro is strongly influenced by the type of extracellular fluid (ECF), blood or lymph, by their high and low flow conditions and transitions between ECFs, and a combination of these parameters. As a result, this in vitro study approaches fluidic and dynamic variations to which NPs are exposed in vivo: different ECF that NPs encounter first in different injection routes, different transitions in-between ECFs during circulation, and simultaneous change in the exposed flow in these transitions. The most-abundant proteins in PCs are found to be not the most abundant in ECFs, but those having high affinity for binding to the surface of NPs. Moreover, some proteins are differently abundant in PCs at different flows, which indicate force-promoted binding, catch bonds. These results suggest that future in vitro studies should consider more complex incubation conditions to improve the in vitro-in vivo consistency necessary for translational research.
在生物环境中，纳米粒子（NPs）的表面会被蛋白质冠（PC）修饰，这决定了它们的生物行为。不幸的是，体外测试得到的 PC 与体内测试不同，导致了体外-体内差异；因此，体外研究并不能说明 NPs 在体内的行为。本研究表明，PC 在体外强烈受到细胞外液（ECF）类型、血液或淋巴、高和低流速条件以及 ECF 之间的转换以及这些参数的组合的影响。因此，这项体外研究接近了 NPs 在体内暴露的流体动力学和动态变化：不同的 ECF，NPs 首先通过不同的注射途径接触，在循环过程中 ECF 之间的不同转换，以及这些转换中暴露流的同时变化。在 PCs 中最丰富的蛋白质不是 ECF 中最丰富的蛋白质，而是那些与 NPs 表面具有高亲和力的蛋白质。此外，一些蛋白质在不同的流速下在 PCs 中的丰度不同，这表明存在力促进结合的黏附键。这些结果表明，未来的体外研究应考虑更复杂的孵育条件，以提高转化研究所需的体外-体内一致性。
