Enhancement of Radio-Thermo-Sensitivity of 5-Iodo-2-Deoxyuridine-Loaded Polymeric-Coated Magnetic Nanoparticles Triggers Apoptosis in U87MG Human Glioblastoma Cancer Cell Line,Cellular and Molecular Bioengineering

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Enhancement of Radio-Thermo-Sensitivity of 5-Iodo-2-Deoxyuridine-Loaded Polymeric-Coated Magnetic Nanoparticles Triggers Apoptosis in U87MG Human Glioblastoma Cancer Cell Line
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2021-06-18 , DOI: 10.1007/s12195-021-00675-y
Samideh Khoei _{1,

2} , Vahid Hosseini ₃ , Mehdi Hosseini ₄ , Sepideh Khoee ₄ , Sakine Shirvalilou _{1,

2} , Seied Rabi Mahdavi ₂ , Jalil Pirayesh Islamian ₃

Affiliation

Introduction

With an emphasis on the radioresistant nature of glioblastoma cells, the aim of the present study was to evaluate the radio-thermo-sensitizing effects of PCL-PEG-coated Superparamagnetic iron oxide nanoparticles (SPIONs) as a carrier of 5-iodo-2-deoxyuridine (IUdR) in monolayer culture of U87MG human glioma cell line.

Methods

Following monolayer culture of U87MG cells, nanoparticle uptake was assessed using Prussian blue staining and ICP-OES method. The U87MG cells were treated with an appropriate concentration of free IUdR and PCL-PEG-coated SPIONs (MNPs) loaded with IUdR (IUdR/MNPs) for 24 h, subjected to hyperthermia (water bath and alternating magnetic field (AMF)) at 43 °C, and exposed to X-ray (2 Gy, 6 MV). The combined effects of hyperthermia with or without magnetic nanoparticles on radiosensitivity of the U87MG cells were evaluated using colony formation assay (CFA) and Flowcytometry.

Results

Prussian blue staining and ICP-OES showed that the nanoparticles were able to enter the cells. The results also indicated that IUdR/MNPs combined with X-ray radiation and hyperthermia significantly decreased the colony formation ability of monolayer cells (1.11, 1.41 fold) and increased the percentage of apoptotic (2.47, 4.1 fold) and necrotic cells (12.28, 29.34 fold), when compared to IUdR combined with X-ray and hyperthermia or IUdR/MNPs + X-ray. MTT results revealed that the presence of IUdR/MNPs significantly increased the toxicity of AMF hyperthermia compared to the water bath method.

Conclusions

Our study showed that SPIONs/PCL-PEG, as a carrier of IUdR, can enhance the cytotoxic effects of radiotherapy and hyperthermia and act as a radio-thermo-sensitizing agent.

Graphic Abstract

中文翻译：

增强 5-Iodo-2-Deoxyuridine 负载的聚合物包覆磁性纳米粒子的放射热敏感性在 U87MG 人胶质母细胞瘤癌细胞系中引发细胞凋亡

介绍

本研究强调胶质母细胞瘤细胞的抗辐射特性，旨在评估 PCL-PEG 涂层超顺磁性氧化铁纳米粒子 (SPIONs) 作为 5-iodo-2- 载体的放射热敏效应。 U87MG 人胶质瘤细胞系单层培养物中的脱氧尿苷 (IUdR)。

方法

在 U87MG 细胞的单层培养后，使用普鲁士蓝染色和 ICP-OES 方法评估纳米颗粒的摄取。U87MG 细胞用适当浓度的游离 IUdR 和 PCL-PEG 包被的 SPIONs (MNPs) 处理 24 小时，负载 IUdR (IUdR/MNPs) 24 小时，在 43 °C，并暴露于 X 射线（2 Gy，6 MV）。使用集落形成测定法 (CFA) 和流式细胞术评估了有或没有磁性纳米粒子的热疗对 U87MG 细胞放射敏感性的综合影响。

结果

普鲁士蓝染色和ICP-OES显示纳米颗粒能够进入细胞。结果还表明，IUdR/MNPs联合X射线照射和热疗显着降低了单层细胞的集落形成能力（1.11、1.41倍），增加了凋亡细胞（2.47、4.1倍）和坏死细胞（12.28、29.34）的百分比。倍），与 IUdR 结合 X 射线和热疗或 IUdR/MNPs + X 射线相比。MTT 结果显示，与水浴法相比，IUdR/MNPs 的存在显着增加了 AMF 热疗的毒性。