当前位置: X-MOL 学术Nano Today › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A multilayered cell culture model for transport study in solid tumors: Evaluation of tissue penetration of polyethyleneimine based cationic micelles
Nano Today ( IF 13.2 ) Pub Date : 2014-12-01 , DOI: 10.1016/j.nantod.2014.10.003
Seiji Miura 1 , Hidenori Suzuki 1 , You Han Bae 2
Affiliation  

Limited drug distribution is partially responsible for the efficacy gap between preclinical and clinical studies of nano-sized drug carriers for cancer therapy. In this study, we examined the transport behavior of cationic micelles formed from a triblock copolymer of poly(D,L-lactide-co-glycolide)-block-branched polyethyleneimine-block-poly(D,L-lactide-co-glycolide) using a unique in vitro tumor model composed of a multilayered cell culture (MCC) and an Ussing chamber system. The Cy3-labeled cationic micelles showed remarkable Cy3 distribution in the MCC whereas charge-shielded micelles with a poly(ethylene glycol) surface accumulated on the surface of the MCC. Penetration occurred against convectional flow caused by a hydraulic pressure gradient. The study using fluorescence resonance energy transfer (FRET) showed that the cationic micelles dissociate at the interface between the culture media and the MCC or possibly inside of the first-layer cells and penetrates into the MCC as unimers. The penetration and distribution were energy-dependent and suppressed by various endocytic inhibitors. These suggest that cationic unimers mainly utilized clathrin-mediated endocytosis and macropinocytosis for cellular entry and a significant fraction were exocytosed by an unknown mechanism.

中文翻译:


用于实体瘤转运研究的多层细胞培养模型:基于聚乙烯亚胺的阳离子胶束的组织渗透评估



有限的药物分布是造成用于癌症治疗的纳米药物载体的临床前和临床研究之间功效差距的部分原因。在这项研究中,我们研究了由聚(D,L-丙交酯-乙交酯)-嵌段支化聚乙烯亚胺-嵌段-聚(D,L-丙交酯-乙交酯)三嵌段共聚物形成的阳离子胶束的传输行为使用由多层细胞培养物 (MCC) 和 Ussing 室系统组成的独特体外肿瘤模型。 Cy3 标记的阳离子胶束在 MCC 中显示出显着的 Cy3 分布,而具有聚乙二醇表面的电荷屏蔽胶束则积聚在 MCC 表面。渗透是在水压梯度引起的对流流动的情况下发生的。使用荧光共振能量转移 (FRET) 的研究表明,阳离子胶束在培养基和 MCC 之间的界面处或可能在第一层细胞内部解离,并作为单聚体渗透到 MCC 中。渗透和分布是能量依赖性的,并被各种内吞抑制剂抑制。这些表明阳离子单聚体主要利用网格蛋白介导的内吞作用和巨胞饮作用进入细胞,并且很大一部分通过未知机制被胞吐。
更新日期:2014-12-01
down
wechat
bug