In vitro and in vivo interactions of selected nanoparticles with rodent serum proteins and their consequences in biokinetics.
In vitro and in vivo interactions of selected nanoparticles with rodent serum proteins and their consequences in biokinetics.
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DOI：
10.3762/bjnano.5.180
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发表时间：
2014
影响因子：
3.1
通讯作者：
Parak WJ
中科院分区：
文献类型：
--
作者：
Kreyling WG;Fertsch-Gapp S;Schäffler M;Johnston BD;Haberl N;Pfeiffer C;Diendorf J;Schleh C;Hirn S;Semmler-Behnke M;Epple M;Parak WJ
当哺乳动物体内的颗粒与体液接触时，它们会与可溶性蛋白质或细胞膜内的蛋白质结合，形成所谓的蛋白质冠。由于不同体液中具有不同亲和力和分数的蛋白质过多以及颗粒表面的化合物和结构的巨大变化，这种结合过程非常复杂且高度动态。有趣的是，就纳米粒子（NP）而言，这种蛋白质冠非常适合提供体液内和跨膜易位的引导载体。这种 NP 易位可能随后导致在各种器官和组织及其各自的细胞类型中积聚，而这些器官和组织预计不会积聚如此微小的异物。由于这种前所未有的纳米颗粒积累，组织和细胞中潜在的不良生物反应不能先验地被忽视，但需要进行彻底的研究。因此，我们研究了血清蛋白与许多工程纳米颗粒的相互作用和蛋白结合动力学，作为其理化特性的函数。在这里，我们通过体外孵化测试表明，不同的工程纳米粒子（聚苯乙烯，元素碳）对选定血清蛋白的结合能力在很大程度上取决于纳米粒子的大小和工程表面修饰的特性。在接下来的尝试中，我们系统地研究了用相同离子配体进行表面修饰的金球（AuNP）尺寸（5、15、80 nm）的影响；以及通过蛋白质组学分析对与血清蛋白的结合进行五种不同表面修饰的 5 nm AuNP。我们发现许多血清蛋白的结合强烈依赖于 AuNP 的理化性质。这些体外结果极大地帮助我们解释了使用相同 NP 在啮齿动物中进行的大量体内生物动力学研究。这些结果表明，不仅理化性质决定了金纳米粒子从摄入器官向血液循环的易位以及随后在次级器官和组织中的积累，而且跨器官膜的转运也取决于金纳米粒子的应用途径。我们的体外蛋白质结合研究支持这样的观点，即观察到的体内生物动力学差异是由 NP 蛋白冠及其在生物体内液体和跨膜易位过程中的动态变化介导的。
When particles incorporated within a mammalian organism come into contact with body fluids they will bind to soluble proteins or those within cellular membranes forming what is called a protein corona. This binding process is very complex and highly dynamic due to the plethora of proteins with different affinities and fractions in different body fluids and the large variation of compounds and structures of the particle surface. Interestingly, in the case of nanoparticles (NP) this protein corona is well suited to provide a guiding vehicle of translocation within body fluids and across membranes. This NP translocation may subsequently lead to accumulation in various organs and tissues and their respective cell types that are not expected to accumulate such tiny foreign bodies. Because of this unprecedented NP accumulation, potentially adverse biological responses in tissues and cells cannot be neglected a priori but require thorough investigations. Therefore, we studied the interactions and protein binding kinetics of blood serum proteins with a number of engineered NP as a function of their physicochemical properties. Here we show by in vitro incubation tests that the binding capacity of different engineered NP (polystyrene, elemental carbon) for selected serum proteins depends strongly on the NP size and the properties of engineered surface modifications. In the following attempt, we studied systematically the effect of the size (5, 15, 80 nm) of gold spheres (AuNP), surface-modified with the same ionic ligand; as well as 5 nm AuNP with five different surface modifications on the binding to serum proteins by using proteomics analyses. We found that the binding of numerous serum proteins depended strongly on the physicochemical properties of the AuNP. These in vitro results helped us substantially in the interpretation of our numerous in vivo biokinetics studies performed in rodents using the same NP. These had shown that not only the physicochemical properties determined the AuNP translocation from the organ of intake towards blood circulation and subsequent accumulation in secondary organs and tissues but also the the transport across organ membranes depended on the route of AuNP application. Our in vitro protein binding studies support the notion that the observed differences in in vivo biokinetics are mediated by the NP protein corona and its dynamical change during AuNP translocation in fluids and across membranes within the organism.
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影响因子：
2.1
作者：
Fertsch-Gapp, Stefanie;Semmler-Behnke, Manuela;Kreyling, Wolfgang G.
通讯作者：
Kreyling, Wolfgang G.
影响因子：
14
作者：
Schaeffler, Martin;Sousa, Fernanda;Krol, Silke
通讯作者：
Krol, Silke
影响因子：
18.3
作者：
Kreyling, Wolfgang G.;Semmler-Behnke, Manuela;Takenaka, Shinji;Moeller, Winfried
通讯作者：
Moeller, Winfried
影响因子：
2.7
作者：
Caballero-Diaz, Encarnacion;Pfeiffer, Christian;Parak, Wolfgang J.
通讯作者：
Parak, Wolfgang J.
影响因子：
8.6
作者：
Kittler, S.;Greulich, C.;Epple, M.
通讯作者：
Epple, M.