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用于辐射癌症治疗中 ROS 形成增强剂的磁性氧化铁和钴铁氧体纳米粒子的体外增强生物相容性和水分散性。

Enhanced In Vitro Biocompatibility and Water Dispersibility of Magnetite and Cobalt Ferrite Nanoparticles Employed as ROS Formation Enhancer in Radiation Cancer Therapy.

机构信息

Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen, Egerlandstr. 3, D-91058, Erlangen, Germany.

Department of Material Science, Institute of Polymer Materials, Friedrich-Alexander University of Erlangen, Martensstr. 7, D-91058, Erlangen, Germany.

出版信息

Small. 2018 May;14(21):e1704111. doi: 10.1002/smll.201704111. Epub 2018 Apr 18.

Abstract

Efficient magnetic reactive oxygen species (ROS) formation enhancing agents after X-ray treatment are realized by functionalizing superparamagnetic magnetite (Fe O ) and Co-ferrite (CoFe O ) nanoparticles with self-assembled monolayers (SAMs). The Fe O and CoFe O nanoparticles are synthesized using Massart's coprecipitation technique. Successful surface modification with the SAM forming compounds 1-methyl-3-(dodecylphosphonic acid) imidazolium bromide, or (2-{2-[2-hydroxy-ethoxy]-ethoxy}-ethyl phosphonic acid provides biocompatibility and long-term stability of the Fe O and CoFe O nanoparticles in cell media. The SAM-stabilized ferrite nanoparticles are characterized with dynamic light scattering, X-ray powder diffraction, a superconducting quantum interference device, Fourier transform infrared attenuated total reflectance spectroscopy, zeta potential measurements, and thermogravimetric analysis. The impact of the SAM-stabilized nanoparticles on the viability of the MCF-7 cells and healthy human umbilical vein endothelial cells (HUVECs) is assessed using the neutral red assay. Under X-ray exposure with a single dosage of 1 Gy the intracellular SAM stabilized Fe O and CoFe O nanoparticles are observed to increase the level of ROS in MCF-7 breast cancer cells but not in healthy HUVECs. The drastic ROS enhancement is associated with very low dose modifying factors for a survival fraction of 50%. This significant ROS enhancement effect by SAM-stabilized Fe O and CoFe O nanoparticles constitutes their excellent applicability in radiation therapy.

摘要

通过用自组装单层(SAM)对超顺磁磁铁矿(Fe3O4)和钴铁氧体(CoFe2O4)纳米粒子进行功能化,实现了 X 射线治疗后高效的磁反应性氧物种(ROS)形成增强剂。使用 Massart 的共沉淀技术合成 Fe3O4 和 CoFe2O4 纳米粒子。成功地用 SAM 形成化合物 1-甲基-3-(十二烷基膦酸)咪唑溴化物或(2-{2-[2-羟基乙氧基]-乙氧基}-乙基膦酸进行表面修饰,为 Fe3O4 和 CoFe2O4 纳米粒子在细胞培养基中的生物相容性和长期稳定性提供了保障。用动态光散射、X 射线粉末衍射、超导量子干涉装置、傅里叶变换衰减全反射光谱、Zeta 电位测量和热重分析对 SAM 稳定的铁氧体纳米粒子进行了表征。使用中性红测定法评估了 SAM 稳定的纳米粒子对 MCF-7 细胞和健康人脐静脉内皮细胞(HUVEC)活力的影响。在 1 Gy 单次剂量的 X 射线照射下,观察到细胞内 SAM 稳定的 Fe3O4 和 CoFe2O4 纳米粒子增加了 MCF-7 乳腺癌细胞中的 ROS 水平,但对健康的 HUVEC 没有影响。ROS 的急剧增强与 50%存活分数的非常低剂量修饰因子有关。SAM 稳定的 Fe3O4 和 CoFe2O4 纳米粒子的这种显著的 ROS 增强效应构成了它们在放射治疗中的优异适用性。

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