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金属有机骨架纳米粒子的蛋白质冠:蛋白质吸附行为及细胞相互作用研究。

Protein corona of metal-organic framework nanoparticals: Study on the adsorption behavior of protein and cell interaction.

机构信息

School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, China.

School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, China.

出版信息

Int J Biol Macromol. 2019 Nov 1;140:709-718. doi: 10.1016/j.ijbiomac.2019.08.183. Epub 2019 Aug 21.

DOI:10.1016/j.ijbiomac.2019.08.183
PMID:31445155
Abstract

Nanoscale metal-organic frameworks (NMOFs) have attracted considerable attention for controlled drug delivery. However, the interaction between nanoparticles and the biological macromolecules of physiological system must be valued because the formed protein corona will endow NMOFs with new biorecognition properties. In this study, we carried out detailed protein adsorption studies in vitro and cell uptake tests of HeLa cells for nanospherical Uio66 and nanooctahedral Uio67. Uio67 with higher binding constants to human serum albumin needed to combine more protein molecules to achieve colloidal stability state than that needed by Uio66, and this phenomenon led Uio67 to aggregate under the same incubation condition due to the formation of a single-layer protein. Uio67 also induced an evident conformation change in protein to stabilize the combination. In particular, the cell uptake efficiencies of the two systems showed a significant thickness dependence on the protein corona. When samples incubated in 10% fetal bovine serum (FBS), the intracellular rate was the highest for both systems, but the rate was not proportional to the FBS concentration. Results of this work are important to the development of the considerable potential NMOFs-based medicals and also provide additional insight into protein corona.

摘要

纳米级金属有机骨架(NMOFs)在控制药物输送方面引起了相当大的关注。然而,必须重视纳米颗粒与生理系统的生物大分子之间的相互作用,因为形成的蛋白质冠将赋予 NMOFs 新的生物识别特性。在这项研究中,我们进行了详细的体外蛋白质吸附研究和 HeLa 细胞摄取测试,分别针对纳米球形 Uio66 和纳米八面体 Uio67。与人血清白蛋白结合常数更高的 Uio67 需要结合更多的蛋白质分子才能达到胶体稳定状态,而这一现象导致 Uio67 在相同的孵育条件下由于单层蛋白质的形成而聚集。Uio67 还诱导蛋白质发生明显的构象变化以稳定结合。特别是,两种系统的细胞摄取效率对蛋白质冠有明显的厚度依赖性。当在 10%胎牛血清(FBS)中孵育样品时,两种系统的细胞内速率均最高,但速率与 FBS 浓度不成比例。这项工作的结果对基于 NMOFs 的医学的巨大潜力的发展非常重要,也为蛋白质冠提供了更多的见解。

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