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改性磁性纳米粒子作为治疗诊断一体化试剂的合成与表征:在健康细胞中的体外安全性评估。

Synthesis and characterization of modified magnetic nanoparticles as theranostic agents: in vitro safety assessment in healthy cells.

机构信息

Inorganic Chemistry Laboratory, Chemistry Department, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou 157 71, Greece; Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", 153 41 Aghia Paraskevi Attikis, Greece.

Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", 153 41 Aghia Paraskevi Attikis, Greece.

出版信息

Toxicol In Vitro. 2021 Apr;72:105094. doi: 10.1016/j.tiv.2021.105094. Epub 2021 Jan 15.

Abstract

Over the past few decades nanotechnology has paved its way into cancer treatment procedures with the use of nanoparticles (NPs) for contrast media and therapeutic agents. Iron based NPs are the most investigated since they can be used for drug delivery, imaging and when magnetically activate employed as local heat sources in cancer hyperthermia. In this work, was performed synthesis, characterization and biological evaluation of different types of iron oxide nanoparticles (mNPs'), as promising material for tumor hyperthermia. The surface of mNPs' has modified with inorganic stabilizing agents to particularly improve characteristics such as their magnetic properties, colloidal stability and biocompatibility. The successful coating of mNPs' was confirmed by morphological and structural characterization by transmission electron microscopy (TEM) and Fourier-Transform Infra-Red spectroscopy (FT-IR), while their hydrodynamic diameter was studied by using Dynamic light scattering (DLS). X-ray Diffraction (XRD) proved that the crystallite phase of mNPs' is the same with the pattern of magnetite. Superparamagnetic behavior and mNPs' response under the application of alternating magnetic field (AMF) were also thoroughly investigated and showed good heating efficiency in magnetic hyperthermia experiments. The contrast ability in magnetic resonance imaging (MRI) is also discussed indicating that mNPs are negative MRI contrast types. Nonetheless the effects of mNPs on cell viability was performed by MTT on human keratinocytes, human embryonic kidney cells, endothelial cells and by hemolytic assay on erythrocytes. In healthy keratinocytes wound healing assay in different time intervals was performed, assessing both the cell migration and wound closure. Endothelial cells have also been studied in functional activity performing capillary morphogenesis. In vitro studies showed that mNPs are safely taken by the healthy cells and do not interfere with the biological processes such as cell migration and motility.

摘要

在过去的几十年中,纳米技术已经为癌症治疗方法铺平了道路,使用纳米粒子(NPs)作为对比剂和治疗剂。铁基 NPs 是研究最多的,因为它们可用于药物输送、成像,并且在磁性激活时可用作癌症热疗中的局部热源。在这项工作中,我们合成、表征和评估了不同类型的氧化铁纳米粒子(mNPs'),作为肿瘤热疗的有前途的材料。mNPs'的表面用无机稳定剂进行了修饰,以特别改善其磁性、胶体稳定性和生物相容性等特性。通过透射电子显微镜(TEM)和傅里叶变换红外光谱(FT-IR)的形态和结构表征,以及动态光散射(DLS)研究其水动力直径,证实了 mNPs'的成功包覆。X 射线衍射(XRD)证明了 mNPs'的晶相与磁铁矿的图案相同。超顺磁性行为和 mNPs'在交变磁场(AMF)下的响应也进行了深入研究,在磁热疗实验中显示出良好的加热效率。还讨论了磁共振成像(MRI)中的对比能力,表明 mNPs 是负性 MRI 对比剂类型。尽管如此,还是通过 MTT 在人角质形成细胞、人胚肾细胞、内皮细胞和红细胞溶血试验上进行了 mNPs 对细胞活力的影响。在不同的时间间隔进行了健康角质形成细胞的伤口愈合试验,评估了细胞迁移和伤口闭合。还研究了内皮细胞在功能活性方面的毛细血管形态发生。体外研究表明,mNPs 被健康细胞安全摄取,并且不会干扰细胞迁移和运动等生物学过程。

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