5-iodo-2-deoxyuridine (IUdR) has been demonstrated to induce an appreciable radiosensitizing effect on glioblastoma patients, but due to the short circulation half-life times and failure to pass through the blood-brain barrier (BBB), its clinical use is limited. Accordingly, in this study, we used magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for IUdR and, evaluated its sensitizing enhancement ratio in combination with a single dose X-ray at clinically megavoltage energies for treatment of C6 glioma rats. Nanoparticles were characterized using Zetasizer and TEM microscopy, and in vitro biocompatibility of nanoparticles was assessed with MTT assay. IUdR/MNPs were intravenously administered under a magnetic field (1.3 T) on day 13 after the implantation of C6 cells. After a day following the injection, rats exposed with radiation (8 Gy). ICP-OES analysis data indicated an effective magnetic targeting, leading to remarkably improved penetration through the BBB. In vivo release analysis with HPLC indicated sustained release of IUdR and, prolonged the lifespan in plasma (P < .01). In addition, our findings revealed a synergistic effect for IUdR/MNPs coupled with radiation, which significantly inhibited the tumor expansion (>100%), prolonged the survival time (>100%) and suppressed the anti-apoptotic response of glioma rats by increasing Bax/Bcl-2 ratio (2.13-fold) in compared with the radiation-only. In conclusion, besides high accumulation in targeted tumor sites, the newly developed IUdR/MNPs, also exhibited the ability of IUdR/MNPs to significantly enhance radiosensitizing effect, improve therapeutic efficacy and increase toxicity for glioma-bearing rats.

中文翻译：

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通过pH响应磁性氧化石墨烯纳米载体增强C6胶质瘤荷瘤大鼠的辐射诱导的细胞凋亡。

5-碘-2-脱氧尿苷（IUdR）已被证明可对胶质母细胞瘤患者产生明显的放射增敏作用，但由于循环半衰期短且无法通过血脑屏障（BBB），因此其临床应用是有限的。因此，在这项研究中，我们使用涂有PLGA聚合物的磁性氧化石墨烯（NGO / SPIONs）纳米粒子作为IUdR的动态纳米载体，并在临床兆伏电压能量下结合单剂量X射线评估了其敏化增强比，以治疗IUdR。 C6神经胶质瘤大鼠。使用Zetasizer和TEM显微镜对纳米粒子进行表征，并通过MTT分析评估纳米粒子的体外生物相容性。植入C6细胞后第13天，在磁场（1.3 T）下静脉内施用IUdR / MNP。注射后一天，大鼠受到辐射（8 Gy）照射。ICP-OES分析数据表明有效的磁性靶向，从而显着提高了通过BBB的渗透性。HPLC的体内释放分析表明IUdR持续释放，并延长了血浆的寿命（P <.01）。此外，我们的研究结果显示，IUdR / MNPs与放射线协同作用，可通过增加放射剂量显着抑制肿瘤扩展（> 100％），延长生存时间（> 100％）并抑制神经胶质瘤大鼠的抗凋亡反应。与仅辐射相比，Bax / Bcl-2比（2.13倍）。综上所述，除了在目标肿瘤部位大量积累外，新开发的IUdR / MNPs还具有IUdR / MNPs显着增强放射增敏作用的能力，