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聚合物纳米粒子的合成和生物学特性影响细胞传递:免疫联系。

Synthetic and biological identities of polymeric nanoparticles influencing the cellular delivery: An immunological link.

机构信息

Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Medical Biomaterials Research Center (MBRC), Tehran University of Medical Sciences, Tehran, Iran.

Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Colloid Interface Sci. 2019 Nov 15;556:476-491. doi: 10.1016/j.jcis.2019.08.060. Epub 2019 Aug 16.

DOI:10.1016/j.jcis.2019.08.060
PMID:31473538
Abstract

Enhanced understanding of bio-nano interaction requires recognition of hidden factors such as protein corona, a layer of adsorbed protein around nano-systems. This study compares the biological identity and fingerprint profile of adsorbed proteins on PLGA-based nanoparticles through nano-liquid chromatography-tandem mass spectrometry. The total proteins identified in the corona of nanoparticles (NPs) with different in size, charge and compositions were classified based on molecular mass, isoelectric point and protein function. A higher abundance of complement proteins was observed in modified NPs with an increased size, while NPs with a positive surface charge exhibited the minimum adsorption for immunoglobulin proteins. A correlation of dysopsonin/opsonin ratio was found with cellular uptake of NPs exposed to two positive and negative Fc receptor cell lines. Although the higher abundance of dysopsonins such as apolipoproteins may cover the active sites of opsonins causing a lower uptake, the correlation of adsorbed dysopsonin/opsonin proteins on the NPs surface has an opposite trend with the intensity of cell uptake. Despite the reduced uptake of corona-coated NPs in comparison with pristine NPs, the dysopsonin/opsonin ratio controlled by the physicochemistry properties of NPs could potentially be used to tune up the cellular delivery of polymeric NPs.

摘要

增强对生物-纳米相互作用的理解需要认识到隐藏因素,如蛋白质冠,即在纳米系统周围吸附的蛋白质层。本研究通过纳流液相色谱-串联质谱比较了不同大小、电荷和组成的 PLGA 基纳米颗粒上吸附蛋白的生物学特征和指纹图谱。根据分子量、等电点和蛋白质功能对大小、电荷和组成不同的纳米颗粒(NPs)冠层中鉴定的总蛋白进行分类。具有较大尺寸的修饰 NPs 中观察到补体蛋白的丰度更高,而带正电荷的 NPs 对免疫球蛋白蛋白的吸附最小。还发现了细胞摄取与 NPs 表面吸附的失调素/调理素比率之间的相关性,这些 NPs 暴露于两种阳性和阴性 Fc 受体细胞系中。尽管载脂蛋白等失调素的丰度较高可能会覆盖调理素的活性位点,导致摄取减少,但 NPs 表面吸附的失调素/调理素蛋白的相关性与细胞摄取强度呈相反趋势。尽管与原始 NPs 相比,涂覆有冠的 NPs 的摄取减少,但由 NPs 的物理化学性质控制的失调素/调理素比率可能被用于调整聚合物 NPs 的细胞递送。

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