Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Razi Drug Research Centre, Iran University of Medical Sciences, Tehran, Iran.
Chem Biol Interact. 2018 Nov 1;295:97-108. doi: 10.1016/j.cbi.2018.08.027. Epub 2018 Aug 28.
To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of -33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p < 0.01). Nanoparticles also had high thermal sensitivities under the alternating magnetic field. In conclusion, we developed magnetic IUdR/NGO/PLGA, which not only achieved to high accumulation at the targeted tumor site by magnetic targeting but also indicated significantly enhanced therapeutic efficiency and toxicity for glioma both in vitro and in vivo. This innovation increases the possibility of improving clinical efficiency of IUdR as a radiosensitizer, or lowering the total drug dose to decrease systemic toxicity.
为了克服胶质母细胞瘤（GBM）中血脑屏障（BBB）带来的障碍，我们研究了多功能纳米粒子的应用，这些纳米粒子由功能化的纳米氧化石墨烯（NGO）片和磁性聚（乳酸-共-乙醇酸）（PLGA）组成，用于Glioma 靶向输送放射增敏剂 5-碘-2-脱氧尿苷（IUdR）。通过 MTT 测定法研究了纳米复合材料的体外生物相容性。在 0.5 T 的外部磁场（EMF）密度下，磁性靶向对荷瘤大鼠体内磁性纳米粒子积累的数量和选择性的体内功效，很容易通过 MRI 进行监测。载有 IUdR 的磁性 NGO/PLGA 纳米粒子的直径为 71.8nm，Zeta 电位为-33.07±0.07mV，药物载量为 3.04±0.46%，具有优越的超顺磁性，饱和磁化强度（Ms）为 15.98 emu/g。此外，普鲁士蓝染色显示出有效的磁性靶向作用，导致 IUdR 的肿瘤抑制效率显著提高。与用缓冲生理盐水、IUdR 和 SPION/IUdR/NGO/PLGA 治疗的大鼠相比，用 IUdR/NGO/SPION/PLGA+MF 治疗的大鼠的肿瘤体积明显减小。最重要的是，我们的数据表明，在目前的磁场下，IUdR/NGO/SPION/PLGA 延长了携带脑肿瘤动物的中位生存时间（38 天，p<0.01）。纳米粒子在交变磁场下也具有较高的热灵敏度。总之，我们开发了磁性 IUdR/NGO/PLGA，它不仅通过磁性靶向实现了在靶向肿瘤部位的高积累，而且还表明了在体外和体内对胶质瘤的治疗效果显著增强，毒性降低。这项创新增加了将 IUdR 作为放射增敏剂提高临床疗效的可能性，或者降低总药物剂量以降低全身毒性的可能性。
