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基于三嗪树状大分子修饰磁性纳米粒子的药物递送的优雅 pH 响应型纳米载体。

Elegant pH-Responsive Nanovehicle for Drug Delivery Based on Triazine Dendrimer Modified Magnetic Nanoparticles.

机构信息

Department of Chemistry, University of Isfahan , Isfahan 81746-73441, Iran.

Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan , Isfahan 81746-73441, Iran.

出版信息

Langmuir. 2017 Aug 29;33(34):8503-8515. doi: 10.1021/acs.langmuir.7b00742. Epub 2017 Aug 15.

Abstract

Owing to properties of magnetic nanoparticles and elegant three-dimensional macromolecule architectural features, dendrimeric structures have been investigated as nanoscale drug delivery systems. In this work, a novel magnetic nanocarrier, generation two (G2) triazine dendrimer modified FeO@SiO magnetic nanoparticles (MNP-G2), was designed, fabricated, and characterized by Fourier transform infrared (FT-IR), thermal gravimetric analysis (TGA), vibrating sample magnetometer (VSM), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The prepared MNP-G2 nanosystem offers a new formulation that combines the unique properties of MNPs and triazine dendrimer as a biocompatible material for biomedical applications. To demonstrate the potential of MNP-G2, the nanoparticles were loaded with methotrexate (MTX), a proven chemotherapy drug. The MTX-loaded MNP-G2 (MNP-G2/MTX) exhibited a high drug-loading capacity of MTX and the excellent ability for controlled drug release. The cytotoxicity of MNP-G2/MTX using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide based assay and MCF-7, HeLa, and Caov-4 cell lines revealed that MNP-G2/MTX was more active against the tumor cells than the free drug in a mildly acidic environment. The results of hemolysis, hemagglutination, and coagulation assays confirmed the good blood safety of MNP-G2/MTX. Moreover, the cell uptake and intracellular distribution of MNP-G2/MTX were studied by flow cytometry analysis and confocal laser scanning microscopy (CLSM). This research suggests that MNP-G2/MTX with good biocompatibility and degradability can be selected as an ideal and effective drug carrier in targeted biomedicine studies especially anticancer applications.

摘要

由于磁性纳米粒子的特性和精致的三维大分子结构特征,树枝状结构已被研究作为纳米级药物传递系统。在这项工作中,设计、制备和表征了一种新型磁性纳米载体,第二代(G2)三嗪树枝状聚合物修饰的 FeO@SiO 磁性纳米粒子(MNP-G2),通过傅里叶变换红外(FT-IR)、热重分析(TGA)、振动样品磁强计(VSM)、场发射扫描电子显微镜(FE-SEM)、透射电子显微镜(TEM)和动态光散射(DLS)进行了表征。所制备的 MNP-G2 纳米系统提供了一种新的配方,将 MNPs 和三嗪树枝状聚合物的独特性质结合在一起,作为一种用于生物医学应用的生物相容性材料。为了证明 MNP-G2 的潜力,将纳米粒子负载甲氨蝶呤(MTX),一种已被证实的化疗药物。负载 MTX 的 MNP-G2(MNP-G2/MTX)表现出高载药量和出色的控释能力。基于 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐的 MNP-G2/MTX 的细胞毒性测定和 MCF-7、HeLa 和 Caov-4 细胞系表明,在弱酸性环境下,MNP-G2/MTX 对肿瘤细胞的活性比游离药物更高。溶血、红细胞凝集和凝血试验的结果证实了 MNP-G2/MTX 的良好血液安全性。此外,通过流式细胞术分析和共聚焦激光扫描显微镜(CLSM)研究了 MNP-G2/MTX 的细胞摄取和细胞内分布。这项研究表明,具有良好生物相容性和可降解性的 MNP-G2/MTX 可以作为靶向生物医学研究,特别是抗癌应用的理想有效药物载体。

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