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

Objective: To investigate the radiosensitization of a newly developed nanopartical modified by hyaluronic acid(HA-Gd2 O3 ) in hepatoma HepG-2 cells.Methods:We used HA and GdCl 3 as precur-sors to synthesize HA-Gd2 O3 by polyol method.HA-Gd2 O3 were characterized by transmission electron mi -croscopy and X-ray diffraction.Inhibition rates of cell proliferation with different concentrations of HA -Gd2 O3 (0 -200 g/mL) at 24 h after treatment were determined by CCK -8 assay.The tissue compatibility of HA-Gd2 O3 was evaluated by histological analysis .The cells were randomly divided to four groups (control, HA-Gd2 O3 , radiation and HA-Gd2 O3 +radiation), and CCK-8 assay and clonogenic assay were used to e-valuate radiosensitization.Results:We fabricated the HA-Gd2 O3 with a diameter of 112 nm and the amor-phous phase structure.Inhibition rates of cell proliferation of HA -Gd2 O3 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-Gd2 O3 was no obvious toxicity to the mouse sus-ceptible organs (liver, heart, spleen, lung, and kidney) showed by histological assessment .Compared with control group, radiation group and HA-Gd2 O3 group, HA-Gd2 O3 +radiation group showed lower inhi -bition rates of cell proliferation and survival fraction (P <0.05).Conclusion:HA-Gd2 O3 was successfully developed, with favorable solubility in water, excellent biocompatibility, no obvious toxicity and effective radiosensitization in hepatoma HepG-2 cells.%目的：制备透明质酸功能化三氧化二钆（HA－Gd2 O3）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－Gd2 O3；通过透射电子显微镜、X 射线衍射仪表征HA－Gd2 O3的理化特性；通过 CCK－8法观察不同浓度的 HA－Gd2 O3（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－Gd2 O3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－Gd2 O3组、照射组、HA－Gd2 O3＋照射组，通过 CCK－8法、克隆形成实验检测 HA－Gd2 O3的放疗增敏作用。结果：成功构建 HA－Gd2 O3；HA－Gd2 O3粒径约112 nm，物相结构无定形；0，25，50，100以及200 mg／L 的 HA－Gd2 O3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－Gd2 O3后，小鼠各重要脏器组织形态未见明显变化；HA－Gd2 O3＋照射组 HepG－2细胞抑制率明显低于对照组、放射组、HA－Gd2 O3组（P ＜0．05）。结论：利用透明质酸修饰成功构建 HA－Gd2 O3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。