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控制蛋白质冠的演变:一种提高壳聚糖基纳米粒子生物分布和半衰期的有效方法。

Controlling evolution of protein corona: a prosperous approach to improve chitosan-based nanoparticle biodistribution and half-life.

机构信息

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Department of Radipharmacy, Faculty of pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Sci Rep. 2020 Jun 15;10(1):9664. doi: 10.1038/s41598-020-66572-y.

Abstract

Protein corona significantly affects in vivo fate of nanoparticles including biodistribution and half-life. Without manipulating the physicochemical properties of nanoparticles with considering their biointerference, attaining effective treatment protocols is impossible. For this reason, protein corona evolution and biodistribution of different chitosan (Ch)-based nanoparticles including Ch and carboxymethyl dextran (CMD)/thiolated dextran (TD) polyelectrolyte complexes (PECs) were studied using highly precious and sensitive methods such as liquid chromatography-mass/mass (LC-MS/MS) spectroscopy and positron emission tomography/computed tomography (PET/CT) scan. The importance of serum presence/absence in culture medium with different pH and corona effect on cellular uptake of PECs investigated by in vitro study. Designed PECs have low amounts of proteins in corona mostly enriched by Apolipoproteins, protein C, hemoglobin subunits, and inter-alpha- trypsin inhibitor that beside improving uptake of nanoparticles, they have low liver uptake and notable heart blood pool accumulation that confirmed the long circulation time of the nanoparticles which is favorable for delivery of nanoparticles to the site of action and achieving required therapeutic effect.

摘要

蛋白质冠显著影响纳米粒子的体内命运,包括生物分布和半衰期。如果不考虑纳米粒子的生物干扰来操纵其物理化学性质,就不可能获得有效的治疗方案。出于这个原因,使用高珍贵和敏感的方法,如液相色谱-质谱/质谱 (LC-MS/MS) 光谱法和正电子发射断层扫描/计算机断层扫描 (PET/CT) 扫描,研究了不同壳聚糖 (Ch) 基纳米粒子(包括 Ch 和羧甲基葡聚糖 (CMD)/巯基葡聚糖 (TD) 聚电解质复合物 (PEC))的蛋白质冠演变和生物分布。通过体外研究研究了血清存在/不存在对不同 pH 值培养基中 PEC 细胞摄取的影响以及对其的冠效应。设计的 PEC 具有低量的蛋白质冠,主要富含载脂蛋白、蛋白 C、血红蛋白亚基和α-胰蛋白酶抑制剂,除了提高纳米粒子的摄取外,它们的肝脏摄取量低,心脏血液池的积累明显,这证实了纳米粒子的长循环时间有利于将纳米粒子递送到作用部位并实现所需的治疗效果。

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