Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers
Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers
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DOI：
10.1021/acsnano.7b00376
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发表时间：
2017-03-01
期刊：
影响因子：
17.1
通讯作者：
Tasciotti, Ennio
中科院分区：
文献类型：
--
作者：
Corbo, Claudia;Molinaro, Roberto;Tasciotti, Ennio
了解纳米颗粒和生物组分之间的界面处发生的相互作用是纳米医学中的一个紧迫挑战，因为它们对纳米颗粒的生物命运有影响。在全身注射纳米颗粒后，由血液成分构建的蛋白质冠围绕载体表面并调节其药代动力学和生物分布。纳米技术中基于仿生学的方法试图模仿自然界中发生的事情，以便将特定的天然功能转移到合成纳米颗粒中。已经开发了几种仿生制剂，由于它们的细胞样特性而显示出上级体内特征。我们最近设计了仿生脂质体，称为leukosomes，它概括了白细胞靶向炎症内皮细胞和逃避免疫系统清除的能力。为了深入了解白细胞体的性质，我们决定在体内研究它们的蛋白质冠。到目前为止，大多数关于蛋白质冠的信息都是通过体外实验获得的，这些实验已经证明在体内最小限度地再现了这种现象。在这里，我们直接显示了一个时间依赖性的定量和定性分析的蛋白质冠吸附在体内的白细胞体和控制脂质体。我们观察到，白细胞体吸收的蛋白质比脂质体少，我们确定了一组蛋白质特异性吸附在白细胞体。此外，我们假设，白细胞体表面的巨噬细胞受体的存在中和了免疫细胞对它们的蛋白质冠介导的摄取。这项工作揭示了仿生载体的蛋白质冠，是少数几个在体内进行冠的研究之一。
Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier's surface and modulates its pharmacokinetics and biodistribution. Biomimicry-based approaches in nanotechnology attempt to imitate what happens in nature in order to transfer specific natural functionalities to synthetic nanoparticles. Several biomimetic formulations have been developed, showing superior in vivo features as a result of their cell-like identity. We have recently designed biomimetic liposomes, called leukosomes, which recapitulate the ability of leukocytes to target inflamed endothelium and escape clearance by the immune system. To gain insight into the properties of leukosomes, we decided to investigate their protein corona in vivo. So far, most information about the protein corona has been obtained using in vitro experiments, which have been shown to minimally reproduce in vivo phenomena. Here we directly show a time-dependent quantitative and qualitative analysis of the protein corona adsorbed in vivo on leukosomes and control liposomes. We observed that leukosomes absorb fewer proteins than liposomes, and we identified a group of proteins specifically adsorbed on leukosomes. Moreover, we hypothesize that the presence of macrophage receptors on leukosomes' surface neutralizes their protein corona-meditated uptake by immune cells. This work unveils the protein corona of a biomimetic carrier and is one of the few studies on the corona performed in vivo.