In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody-Targeted Lipid Bilayer Nanoscale Vesicles
In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody-Targeted Lipid Bilayer Nanoscale Vesicles
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DOI：
10.1021/acsnano.5b03300
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发表时间：
2015-08-01
期刊：
影响因子：
17.1
通讯作者：
Kostarelos, Kostas
中科院分区：
文献类型：
--
作者：
Hadjidemetriou, Marilena;Al-Ahmady, Zahraa;Kostarelos, Kostas
蛋白质的吸附及其在纳米颗粒表面上的分层被称为“蛋白质冠”。在许多不同的纳米颗粒与血浆蛋白的体外孵育之后，已经广泛地研究了蛋白质吸附的这种动态过程。然而，蛋白质冠的形成下的动态，在体内条件下仍然在很大程度上未被探索。外推体外形成的蛋白质冠来预测体内纳米颗粒的命运和可能的毒理学负担是非常感兴趣的。然而，临床上使用的纳米颗粒完全缺乏这样的直接比较，使得体外和体内形成的蛋白质冠的研究非常重要。我们的目的是基于构成抗癌剂Doxil的聚乙二醇化脂质体制剂的组成，研究在静脉注射的临床使用的脂质体上形成的体内蛋白质冠。在注射后10 min从CD-1小鼠的血液循环中回收脂质体后，测定体内蛋白质冠的形成。相比之下，通过在CD-1小鼠血浆中孵育脂质体形成体外蛋白质冠。在体内和体外形成的蛋白质冠的形态，组成和细胞内化进行了比较。还比较研究了相同脂质组成的裸（非聚乙二醇化）和单克隆抗体（19 G）靶向脂质体上的蛋白质冠。一个网络的线性结构构成了在体外形成的蛋白质冠，而在体内冠有不同的形态，但没有出现完全包覆脂质体表面。即使附着在循环脂质体上的蛋白质总量与体外孵育中观察到的蛋白质总量相关，但体内冠中的分子种类的多样性要宽得多。在体外和体内形成的蛋白质冠被发现显着减少受体结合和抗体缀合的脂质体的细胞内化;然而，在体内冠的形成并没有导致其靶向能力的完全消融。
The adsorption of proteins and their layering onto nanoparticle surfaces has been called the "protein corona". This dynamic process of protein adsorption has been extensively studied following in vitro incubation of many different nanoparticles with plasma proteins. However, the formation of protein corona under dynamic, in vivo conditions remains largely unexplored. Extrapolation of in vitro formed protein coronas to predict the fate and possible toxicological burden from nanoparticles in vivo is of great interest. However, complete lack of such direct comparisons for clinically used nanoparticles makes the study of in vitro and in vivo formed protein coronas of great importance. Our aim was to study the in vivo protein corona formed onto intravenously injected, clinically used liposomes, based on the composition of the PEGylated liposomal formulation that constitutes the anticancer agent Doxil. The formation of in vivo protein corona was determined after the recovery of the liposomes from the blood circulation of CD-1 mice 10 min postinjection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalization. The protein coronas on bare (non-PEGylated) and monoclonal antibody (19G) targeted liposomes of the same lipid composition were also comparatively investigated. A network of linear fibrillary structures constituted the in vitro formed protein corona, whereas the in vivo corona had a different morphology but did not appear to coat the liposome surface entirely. Even though the total amount of protein attached on circulating liposomes correlated with that observed from in vitro incubations, the variety of molecular species in the in vivo corona were considerably wider. Both in vitro and in vivo formed protein coronas were found to significantly reduce receptor binding and cellular internalization of antibody-conjugated liposomes; however, the in vivo corona formation did not lead to complete ablation of their targeting capability.