睾酮分子印迹磁性纳米材料作为去雄药物对雄性激素依赖型前列腺癌的治疗作用

The treatment of testosterone molecularly imprinted magnetic nanomaterials for androgen dependent prostate cancer as castration treatment

目的探讨睾酮分子印迹磁性纳米粒子(Fe3O4@TSTO-MIPs)作为雄激素依赖型前列腺癌去雄治疗新型药物的可行性。方法以溶胶凝胶法制备的Fe3O4@TSTO-MIPs作为去雄药物;以人前列腺癌雄激素依赖LNCaP细胞和非依赖C4-2细胞为研究对象,分别进行四组处理:①空白对照组:正常培养基,不处理;②去雄处理组:去雄培养基,不处理;③阳性对照组:正常培养基,20 nmol/L临床应用的前列腺癌去势药物MDV3100处理;④实验组:正常培养基,160μg/ml睾酮分子印迹纳米粒子处理。采用细胞免疫荧光试验检测各组细胞雄激素受体(androgen receptor,AR)活性变化,采用流式细胞技术检测其对细胞周期的影响。结果Fe3O4@TSTO-MIPs具有高吸附能力(6.96μg/mg)和高选择性[选择性系数(SC)=3.03];与细胞共同培养,Fe3O4@TSTO-MIPs可自由进入细胞,且24 h后细胞状态仍良好;与空白对照组比较,药物处理后的LNCaP细胞AR入核活性被抑制,细胞周期出现明显阻滞;C4-2细胞的AR入核活性虽被抑制,但未出现细胞周期阻滞。结论Fe3O4@TSTO-MIPs抑制雄激素依赖前列腺癌细胞的生长,其作用机制可能与直接去除前列腺癌细胞内的睾酮有关,去雄能力与MDV3100相当。

Objective To investigate the feasibility of testosterone molecularly imprinted magnetic nanoparticles(Fe3O4@TSTO-MIPs)as a novel drug for the castration treatment of androgen dependent prostate cancer.Methods Fe3O4@TSTO-MIPs was prepared by sol-gel method.Androgen-dependent LNCaP cells and non-dependent C4-2 cells were divided into four groups:①blank control group:normal medium,without treated;②castration treatment group:castration medium,without treated;③positive control group:normal medium,treated with 20 nmol/L MDV3100;④experimental group:normal medium,treated with 160μg/ml MIPs.The androgen receptor(AR)activity of cells in each group was detected by cell immunofluorescence assay,and the effect of cell cycle was detected by flow cytometry.Results Fe3O4@TSTO-MIPs have high adsorption capacity(6.96μg/mg)and high selectivity(SC=3.03).It can enter cells freely after co-culture with cells,and the cell state is still good after 24 h.Compared with the blank control group,the AR activity of drug-treated LNCaP cells was inhibited and cell cycle was significantly blocked.Although the AR nucleation activity of C4-2 cells was inhibited,no cell cycle arrest was observed.Conclusion Fe3O4@TSTO-MIPs inhibits the growth of androgen-dependent prostate cancer cells,and its mechanism may be related to the direct removal of testosterone in prostate cancer cells.The castration ability is equivalent to that of MDV3100.