聚乙二醇修饰的5-氟尿嘧啶磁性白蛋白微球联合恒定外磁场对体外人结肠癌细胞生长的抑制作用

目的探讨聚乙二醇修饰的磁性5-氟尿嘧啶白蛋白微球(PEG-5-FU-MAMS)联合恒定外磁场体外对人结肠癌(LoVo)细胞生长的抑制作用及其机制。 方法采用乳化-加热固化法制备PEG-5-FU-MAMS，并检测其表征，将体外培养的LoVo细胞分为4组：A组为PEG-5-FU-MAMS联合磁场组；B组为PEG-5-FU-MAMS组；C组为游离5-氟尿嘧啶(5-FU)组；D组为单纯磁场组。参照5-FU血浆峰水平10.0 mg/L，每组设含5-FU水平为1.0，2.0，5.0，10.0，20.0，50.0，100.0 mg/L 7种不同的药物和微球备用。每种条件重复3孔，采用噻唑蓝(MTT)比色分析法测定各组肿瘤细胞生长抑制率(IR)，观察PEG-5-FU-MAMS联合恒定磁场组对体外LoVo细胞生长的抑制作用。 结果微球平均粒径为(1.32±0.50)μm，呈球形，表面光滑，载药量为(5.31±0.13)%，具有良好的磁响应性和缓释性。LoVo细胞培养24 h后，显微镜下各组肿瘤细胞完全贴壁，生长良好，折光性好。单纯磁场组体外对LoVo细胞生长无明显影响。经过不同的处理后，含5-FU浓度为20.0，50.0，100.0 mg/L时，B组和C组IR>50%，药物敏感，两组在相应药物浓度下IR相似，差异无统计学意义(q＝2.02，2.11，2.74；P>0.05)。在含5-FU浓度为10.0 mg/L时，A组IR为59.8%，IR>50%，药物敏感，且随着药物浓度的增高，IR逐步升高，与B、C组比较，差异有统计学意义(F＝62.09，66.74，56.62，66.13；P<0.05)。 结论PEG-5-FU-MAMS具有良好的外形、粒径、载药量、磁响应性和药物缓释作用；PEG-5-FU-MAMS联合恒定外磁场能显著增强对LoVo细胞生长的抑制效应。

The growing inhibition action of PEG modified magnetic 5-Fluorouracil albumin microspheres combined with constant external magnetic fields on human colon carcinoma LoVo cells in vitro

ObjectiveTo investigate the growth inhibiting action of PEG modified magnetic 5-Fluorouracil albumin microspheres (PEG-5-FU-MAMS) combined with constant external magnetic fields on human colorectal carcinoma LoVo cells in vitro and the mechanism. MethodsThe PEG-5-FU-MAMS were prepared by emulsification/solidification method.The cultured LoVo cells were divided into four groups.Group A was processed with PEG-5-FU-MAMS combined with external magnetic fields, group B was PEG-5-FU-MAMS without magnetic fields, group C was free 5-FU, group D was pure magnetic field.The growth of LoVo cells was observed under an inverted microscopy, and the inhibitory rate (IR) was assayed by methyl thiazol tetrazolium (MTT) assay. ResultsThe obtained microspheres (MS) were spherical and about (1.32±0.50)μm in size.The drug loading was (5.31±0.13)% and the MS had good magnetic responsibility.The release rate of 5-Fu in vitro showed that PEG-5-FU-MAMS had pronounced sustained-release effect.LoVo cells grew well and had good refraction after 24 h. Under the microscope, tumor cells were completely adherent.After different treatment, the tumor growth showed no difference on tumor cells in pure magnetic group.The IR of pure PEG-5-FU-MAMS group and free 5-FU group at same drug concentration were similar, there were no significant differences between them(q=2.02, 2.11, 2.74; P>0.05). Compared with pure PEG-5-FU-MAMS and free 5-FU group, when the concentration of 5-FU exceeded 10.0 mg/L, IR was significantly increased after PEG-5-FU-MAMS combined with constant external magnetic fields(F=62.09, 66.74, 56.62, 66.13; P<0.05). ConclusionsPEG-5-FU-MAMS is characterized with good shape, particle size, drug loading, magnetic responsibility and drug release.The growth inhibiting action is significantly enhanced after PEG-5-FU-MAMS combined with constant external magnetic fields.