Laboratory for Radioisotopes, Vinča Institute of Nuclear Sciences, University of Belgrade, P. O. Box 522, 11001 Belgrade, Serbia.
Laboratory for Radioisotopes, Vinča Institute of Nuclear Sciences, University of Belgrade, P. O. Box 522, 11001 Belgrade, Serbia.
Mater Sci Eng C Mater Biol Appl. 2019 Sep;102:124-133. doi: 10.1016/j.msec.2019.04.034. Epub 2019 Apr 13.
Novel theranostic nanoplatform is expected to integrate imaging for guiding and monitoring of the tumor therapy with great therapeutic efficacy and fewer side effects. Here we describe the preparation of a multifunctional Tc-bisphosphonate-coated magnetic nanoparticles (MNPs) based on FeO and coated with two hydrophilic bisphosphonate ligands, i.e., methylene diphosphonate (MDP) and 1-hydroxyethane-1,1- diphosphonate (HEDP). The presence of the bisphosphonates on the MNPs surface, enabled their biocompatibility, colloidal stability and successful binding of the radionuclide. The morphology, size, structure, surface charge and magnetic properties of obtained bisphosphonate-coated FeO MNPs were characterized by transmission electron microscopy, X-ray powder diffraction, dynamic light scattering, laser Doppler electrophoresis, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The specific power absorption values for FeO-MDP and FeO-HEDP were 113 W/g and 141 W/g, respectively, indicated their heating ability under applied magnetic field. Coated MNPs were radiolabeled with Tc using stannous chloride as the reducing agent in a reproducible high yield (95% for FeO-MDP and 97% for FeO-HEDP MNPs) and were remained stable in saline and human serum for 24 h. Ex vivo biodistribution studies presented significant liver and spleen uptake in healthy Wistar rats after intravenous administration at all examined time points due to the colloidal nature of both Tc-MNPs. Results of scintigraphy studies are in accordance with ex vivo biodistribution studies, demonstrating high in vivo stability of radiolabeled MNPs and therefore results of both methods were proved as accurate information on the biodistribution profile of investigated MNPs. Overall, in vitro and in vivo stability as well as heating ability, indicate that biocompatible radiolabeled bisphosphonate magnetic nanoparticles exhibit promising potential as a theranostic nanoagent.
新型治疗诊断一体化纳米平台有望将肿瘤治疗的成像指导和监测与高治疗效果和较少的副作用相结合。在这里,我们描述了一种基于 FeO 的多功能 Tc-双膦酸盐涂层磁性纳米颗粒(MNPs)的制备,该纳米颗粒用两种亲水性双膦酸盐配体,即亚甲基二膦酸盐(MDP)和 1-羟乙叉二膦酸盐(HEDP)进行了涂层。MNPs 表面存在双膦酸盐,使其具有生物相容性、胶体稳定性和放射性核素的成功结合。通过透射电子显微镜、X 射线粉末衍射、动态光散射、激光多普勒电泳、傅里叶变换红外光谱和振动样品磁强计对所得双膦酸盐涂层 FeO MNPs 的形态、尺寸、结构、表面电荷和磁性能进行了表征。FeO-MDP 和 FeO-HEDP 的比吸收功率分别为 113 W/g 和 141 W/g,表明它们在施加磁场下的加热能力。用氯化亚锡作为还原剂,用 Tc 对涂层 MNPs 进行放射性标记,在所有检查时间点,FeO-MDP 和 FeO-HEDP MNPs 的放射性标记产率均为 95%和 97%,且在生理盐水和人血清中 24 小时内保持稳定。在健康的 Wistar 大鼠中,静脉注射后,由于两种 Tc-MNPs 的胶体性质,在所有检查时间点均观察到明显的肝和脾摄取。闪烁显像研究的结果与体外生物分布研究一致,证明放射性标记 MNPs 在体内具有高稳定性,因此两种方法的结果均被证明是关于所研究 MNPs 的生物分布情况的准确信息。总之,体外和体内稳定性以及加热能力表明,生物相容的放射性标记双膦酸盐磁性纳米颗粒作为治疗诊断一体化纳米试剂具有很大的应用潜力。
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