The effects of aggregation and protein corona on the cellular internalization of iron oxide nanoparticles
The effects of aggregation and protein corona on the cellular internalization of iron oxide nanoparticles
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DOI：
10.1016/j.biomaterials.2011.08.048
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发表时间：
2011-12-01
期刊：
影响因子：
14
通讯作者：
Berret, J. -F.
中科院分区：
文献类型：
--
作者：
Safi, M.;Courtois, J.;Berret, J. -F.
工程无机纳米颗粒是纳米技术发展的重要组成部分。在纳米医学中的应用中，需要对颗粒进行功能化处理，以确保其在生物体液中具有良好的分散性。然而，在许多情况下，功能化是不够的：颗粒要么被血清蛋白质的电晕包裹，要么从溶剂中沉淀出来。在本文中，我们发现，通过将纳米氧化铁的包覆层从低分子量配体(柠檬酸离子)改为小分子羧化聚合物(聚丙烯酸)，分散体的胶体稳定性得到了提高，铁对活哺乳动物细胞的吸附/内化受到了深刻的影响。柠檬酸盐包裹的颗粒在所有测试的基于胎儿-小牛血清的生理条件下都被证明是不稳定的，而聚合物包裹的颗粒表现出出色的分散性以及没有蛋白质电晕的结构。用透射电子显微镜和流式细胞仪研究了纳米粒子与人淋巴母细胞的相互作用。文中强调了两种类型的纳米颗粒/细胞相互作用。铁氧化物被发现要么吸附在细胞膜上，要么内化到膜结合的内吞间隔中。对于被柠檬酸盐包覆的沉淀粒子，相互作用的动力学表明，氧化铁在细胞表面大量而快速地吸附。根据细胞学数据对吸附铁和内化铁之间的分配进行了定量。这些结果突出了弹性吸附纳米材料在细胞质膜上的重要性。(C)2011爱思唯尔有限公司。保留所有权利。
Engineered inorganic nanoparticles are essential components in the development of nanotechnologies. For applications in nanomedicine, particles need to be functionalized to ensure a good dispersibility in biological fluids. In many cases however, functionalization is not sufficient: the particles become either coated by a corona of serum proteins or precipitate out of the solvent. In the present paper, we show that by changing the coating of iron oxide nanoparticles from a low-molecular weight ligand (citrate ions) to small carboxylated polymers (poly(acrylic acid)), the colloidal stability of the dispersion is improved and the adsorption/internalization of iron toward living mammalian cells is profoundly affected. Citrate-coated particles are shown to destabilize in all fetal-calf-serum based physiological conditions tested, whereas the polymer coated particles exhibit an outstanding dispersibility as well as a structure devoid of protein corona. The interactions between nanoparticles and human lymphoblastoid cells are investigated by transmission electron microscopy and flow cytometry. Two types of nanoparticle/cell interactions are underlined. Iron oxides are found either adsorbed on the cellular membranes, or internalized into membrane-bound endocytosis compartments. For the precipitating citrate-coated particles, the kinetics of interactions reveal a massive and rapid adsorption of iron oxide on the cell surfaces. The quantification of the partition between adsorbed and internalized iron was performed from the cytometry data. The results highlight the importance of resilient adsorbed nanomaterials at the cytoplasmic membrane. (C) 2011 Elsevier Ltd. All rights reserved.