透明质酸功能化三氧化二钆纳米颗粒的制备及其放疗增敏作用

［摘要］目的: 制备透明质酸功能化三氧化二钆（HA Gd2O3）纳米颗粒，探讨其对肝癌HepG 2细胞的放疗增敏作用。方法: 利用透明质酸、氯化钆为前驱物通过聚醇水热法制备HA Gd2O3；通过透射电子显微镜、X射线衍射仪表征HA Gd2O3的理化特性；通过CCK 8法观察不同浓度的HA Gd2O3（0～200 mg/L）作用24 h后肝癌细胞的细胞活性；通过HE染色分析HA Gd2O3静注后小鼠各脏器病理学结构的变化；根据实验要求将细胞随机分为对照组、HA Gd2O3组、照射组、HA Gd2O3+照射组，通过CCK 8法、克隆形成实验检测HA Gd2O3的放疗增敏作用。结果： 成功构建HA Gd2O3；HA Gd2O3粒径约112 nm，物相结构无定形；0，25，50，100以及200 mg/L的HA Gd2O3对HepG 2细胞的增殖抑制率分别为0%，(0.640±0.024)%，（3.943±0.063）%，(4.871±0.062)%和（4.084±0.076）%，各浓度间抑制率差异无统计学意义（P<0.05）；静注HA Gd2O3后，小鼠各重要脏器组织形态未见明显变化；HA Gd2O3+照射组HepG 2细胞抑制率明显低于对照组、放射组、HA Gd2O3组（P<0.05）。结论： 利用透明质酸修饰成功构建HA Gd2O3纳米颗粒，其具有良好的水溶性、生物相容性，对HepG 2细胞具有显著放疗增敏作用。

Hyaluronic acid functionalized gadolinium oxide nanoparticles for radiosensitization enhancements

［Abstract］Objective To investigate the radiosensitization of a newly developed nanopartical modified by hyaluronic acid(HA Gd2O3) in hepatoma HepG 2 cells. MethodsWe used HA and GdCl3 as precursors to synthesize HA Gd2O3 by polyol method. HA Gd2O3 were characterized by transmission electron microscopy and X ray diffraction.Inhibition rates of cell proliferation with different concentrations of HA Gd2O3 (0-200 g/mL) at 24 h after treatment were determined by CCK 8 assay. The tissue compatibility of HA Gd2O3 was evaluated by histological analysis. The cells were randomly divided to four groups (control, HA Gd2O3, radiation and HA Gd2O3 + radiation), and CCK 8 assay and clonogenic assay were used to evaluate radiosensitization. ResultsWe fabricated the HA Gd2O3 with a diameter of 112 nm and the amorphous phase structure. Inhibition rates of cell proliferation of HA Gd2O3 ranging from 0, 25, 50, 100, 200 mg/L were 0%, (0.640±0.024)%, (3.943±0.063)%, (4.871±0.062)%, and (4.084±0.076)% with no significant differences(P>0.05). HA Gd2O3 was no obvious toxicity to the mouse susceptible organs (liver, heart, spleen, lung, and kidney) showed by histological assessment. Compared with control group, radiation group and HA Gd2O3 group, HA Gd2O3+radiation group showed lower inhibition rates of cell proliferation and survival fraction (P<0.05). ConclusionHA Gd2O3 was successfully developed, with favorable solubility in water, excellent biocompatibility, no obvious toxicity and effective radiosensitization in hepatoma HepG-2 cells.