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载紫杉醇的荧光磁性 PEI-PLGA 纳米粒用于人脑癌细胞的细胞成像、增强凋亡和自噬。

Fluorescent magnetic PEI-PLGA nanoparticles loaded with paclitaxel for concurrent cell imaging, enhanced apoptosis and autophagy in human brain cancer.

机构信息

College of Bioengineering, Henan University of Technology, Zhengzhou, Henan 450001, PR China.

College of Bioengineering, Henan University of Technology, Zhengzhou, Henan 450001, PR China.

出版信息

Colloids Surf B Biointerfaces. 2018 Dec 1;172:708-717. doi: 10.1016/j.colsurfb.2018.09.033. Epub 2018 Sep 16.

Abstract

Magnetic nanoparticles are regarded as a promising drug delivery vehicle with the improved efficacy and lowered side effects for antitumor therapy. Herein, the poly lactic-co-glycolic acid (PLGA) modified magnetic nanoplatform was synthesized using superparamagnetic γ-FeO nanoparticles (MNPs) as a core, and then labelled with polyethylenimine (PEI)-conjugated fluorescein isothiocyanate (FITC), and simultaneously loaded with antitumor drug paclitaxel (PTX) for theranostic analysis of antitumor effects investigated in human brain glioblastoma U251 cells. As a result, the prepared PEI-PLGA-MNPs showed a relatively round sphere with an average size of 80 nm approximately, and the FITC-labeling PEI-PLGA-MNPs were efficiently endocytosed by the U251 cells for cellular imaging. Moreover, the fabricated PEI-PLGA-PTX-MNPs also demonstrated an inhibition of the targeted cell proliferation and migration, and a programmed cell death, via both apoptosis modulating by a burst of reactive oxygen species (ROS) and autophagy with accumulation of autophagosomes and LC3-II signals detected in the treated glioblastoma U251 cells after uptaking. Therefore, the constructed nanoplatform could be effectively applied for simultaneous cellular imaging and drug delivery in human brain glioblastoma treatment in future.

摘要

磁性纳米粒子被认为是一种很有前途的药物输送载体,可提高抗肿瘤治疗的疗效,降低副作用。在此,我们使用超顺磁性 γ-FeO 纳米粒子 (MNPs) 作为核心,合成了聚乳酸-共-羟基乙酸 (PLGA) 修饰的磁性纳米平台,然后用聚乙二胺 (PEI)-缀合的异硫氰酸荧光素 (FITC) 标记,并同时装载抗肿瘤药物紫杉醇 (PTX),用于人脑神经胶质瘤 U251 细胞的抗肿瘤效果的诊断和治疗分析。结果表明,所制备的 PEI-PLGA-MNPs 呈相对较圆的球体,平均粒径约为 80nm,FITC 标记的 PEI-PLGA-MNPs 被 U251 细胞高效内吞用于细胞成像。此外,所构建的 PEI-PLGA-PTX-MNPs 还通过 ROS 爆发调节的细胞凋亡和自噬,以及在摄取后的处理神经胶质瘤 U251 细胞中检测到自噬体和 LC3-II 信号的积累,显示出对靶细胞增殖和迁移的抑制作用和程序性细胞死亡。因此,该纳米平台可有效地用于人脑神经胶质瘤治疗中的细胞成像和药物联合递送。

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