Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles
Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles
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DOI：
10.1016/j.jconrel.2009.01.018
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发表时间：
2009-05-05
影响因子：
10.8
通讯作者：
Jeong, Seo Young
中科院分区：
文献类型：
--
作者：
Nam, Hae Yun;Kwon, Seok Min;Jeong, Seo Young
基于聚合物纳米颗粒的载体有望将治疗药物定向输送到细胞内的作用部位。为了优化给药效果，通常需要调整物理化学性质(即颗粒大小、形状、表面电荷、亲脂性等)。是必要的，以每种类型的纳米颗粒特有的方式。最近的研究表明，疏水修饰的乙二醇壳聚糖纳米粒(HGC)通过增强渗透性和保留率(EPR)效应，可以有效地靶向肿瘤。作为一项持续的努力，本文报道了HGC纳米颗粒的细胞摄取机制和细胞内命运的研究。由乙二醇壳聚糖(GC)的游离氨基与5-β-胆酸部分衍生化得到的HGC纳米颗粒呈球形，平均粒径为359 nm，Zeta电位约为22 mV。有趣的是，与亲水性GC聚合物相比，这些纳米颗粒在整个细胞中的分布增强。体外内吞抑制实验表明，几种不同的摄取途径(例如，网状蛋白介导的内吞作用、小凹介导的内吞作用和巨饮饮作用)参与了HGC的内化。通过透射电子显微镜和共定位研究，发现一些HGC纳米颗粒在进入溶酶体时被包裹在溶酶体内。由于我们的HGC纳米颗粒具有低毒、生物相容性好、可被多种非破坏性的细胞内途径快速吸收等优点，因此我们的HGC纳米颗粒可作为一种多功能的细胞内给药载体。(C)2009爱思唯尔B.V.保留所有权利。
Polymeric nanoparticle-based carriers are promising agents for the targeted delivery of therapeutics to the intracellular site of action. To optimize the efficacy in delivery, often the tuning of physicochemical properties (i.e., particle size, shape, surface charge, lipophilicity, etc.) is necessary, in a manner specific to each type of nanoparticle. Recent studies showed an efficient tumor targeting by hydrophobically modified glycol chitosan (HGC) nanoparticles through the enhanced permeability and retention (EPR) effect. As a continued effort, here the investigations on the cellular uptake mechanism and the intracellular fate of the HGC nanoparticles are reported. The HGC nanoparticle, prepared by a partial derivatization of the free amino groups of glycol chitosan (GC) with 5 beta-cholanic acid, had a globular shape with the average diameter of 359 nm and the zeta potential of ca. 22 mV. Interestingly, these nanoparticles showed an enhanced distribution in the whole cells, compared to the parent hydrophilic GC polymers. In vitro experiments with endocytic inhibitors suggested that several distinct uptake pathways (e.g., clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macro pinocytosis) are involved in the internalization of HGC. Some HGC nanoparticles were found entrapped in the lysosomes upon entry, as determined by TEM and colocalization studies. Given such favorable properties including low toxicity, biocompatibility, and fast uptake by several nondestructive endocytic pathways, our HGC nanoparticles may serve as a versatile carrier for the intracellular delivery of therapeutic agents. (c) 2009 Elsevier B.V. All rights reserved.