CEINGE-Biotecnologie Avanzate s.c.a r.l. , Via G. Salvatore 486, Naples, 80145, Italy.
Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , Galveston, Texas 77555, United States.
ACS Nano. 2017 Mar 28;11(3):3262-3273. doi: 10.1021/acsnano.7b00376. Epub 2017 Mar 10.
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.
理解纳米粒子与生物成分之间界面发生的相互作用是纳米医学中的一个紧迫挑战，因为它们会影响纳米粒子的生物命运。在将纳米粒子全身注射后，由血液成分构成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。纳米技术中的仿生学方法试图模仿自然界中发生的情况，以便将特定的自然功能转移到合成纳米粒子上。已经开发出了几种仿生配方，由于其类似细胞的特性，它们表现出了优越的体内特性。我们最近设计了仿生脂质体，称为白细胞体，它们再现了白细胞靶向炎症内皮并逃避免疫系统清除的能力。为了深入了解白细胞体的特性，我们决定研究其体内的蛋白质冠。到目前为止，关于蛋白质冠的大多数信息都是通过体外实验获得的，这些实验已经表明，它们很少能再现体内现象。在这里，我们直接展示了对体内吸附在白细胞体和对照脂质体上的蛋白质冠进行的时间依赖性定量和定性分析。我们观察到白细胞体吸附的蛋白质比脂质体少，并且我们鉴定出一组特异性吸附在白细胞体上的蛋白质。此外，我们假设白细胞体表面的巨噬细胞受体的存在可以中和其由蛋白质冠介导的免疫细胞摄取。这项工作揭示了仿生载体的蛋白质冠，是为数不多的在体内进行的冠研究之一。
