叶酸磁性纳米颗粒载顺铂抑制人喉癌Hep-2细胞生长且无细胞毒性作用  

Folic acid magnetic nanoparticles containing cisplatin inhibit the growth of human laryngeal cancer Hep-2 cells in a non-cytotoxic manner

作　　者：张海中[1] 黄爱萍[2] 

机构地区：[1]河北医科大学第二医院耳鼻喉科,河北省石家庄市050000 [2]河北省儿童医院耳鼻喉科,河北省石家庄市050031

出　　处：《中国组织工程研究》2016年第8期1111-1117,共7页Chinese Journal of Tissue Engineering Research

基　　金：河北省医学科学研究重点课题计划指令性课题(ZL20140084)~~

摘　　要：背景:化疗药物对癌细胞和对正常组织细胞均有杀伤作用,分子靶向治疗可以减少或者避免化疗药物对正常细胞的毒副反应。目的:观察叶酸磁性纳米颗粒载顺铂对喉癌的治疗作用。方法:制备叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒,将叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒、顺铂以及不含顺铂叶酸磁性纳米颗粒与人喉癌Hep-2细胞共培养,用MTT、流式细胞仪以及透射电镜观察的方法检测体外叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒、顺铂以及叶酸修饰的醛基化海藻酸钠改性磁性纳米颗粒对人喉癌Hep-2细胞的影响。结果与结论:1叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒和顺铂均对人喉癌Hep-2细胞有抑制作用,且两组抑制率比较差异无显著性意义(P>0.05)。2叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒和顺铂两种药物随着顺铂药物浓度的增加,对人喉癌Hep-2细胞的抑制率逐渐升高。3顺铂在24,48 h对Hep-2作用的半抑制浓度值比较差异有显著性意义(P<0.05)。4叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒和顺铂与Hep-2培养均引起细胞凋亡,凋亡细胞数量随着药物浓度的增加而增加(P<0.05),但两种药物之间比较差异无显著性意义(P>0.05)。5叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒和顺铂均在低浓度时G0/G1期细胞比例增加,S,G2/M其细胞比例降低(P<0.05)。6透射电镜检测结果显示,摄取叶酸修饰的载顺铂醛基化海藻酸钠改性磁性纳米颗粒的细胞出现了显著的凋亡崩解改变。7结果说明,叶酸磁性纳米颗粒载顺铂可抑制人喉癌Hep-2细胞的生长,且不影响顺铂的药效,对细胞无毒性作用。BACKGROUND： Chemotherapy drugs can kill both cancer cells and normal tissue cells. Molecular targeted therapy can reduce or avoid toxicity of chemotherapy drugs to normal cells. OBJECTIVE： To study the therapeutic effect of folic acid magnetic nanoparticles containing cisplatin on laryngeal cancer. METHODS： Folic acid-cis-diaminodichloroplatinum（II）-aldehyde sodium alginate-magnetic nanoparticles（FA-CDDP-ASA-MNPs） were prepared. The FA-CDDP-ASA-MNPs, CDDP and FA-ASA-MNPs were cultured together with human laryngeal cancer Hep-2 cells. To detect the effect of FA-CDDP-ASA-MNPs, CDDP and FA-ASA-MNPs on human laryngeal cancer Hep-2 cells, MTT, flow cytometry and transmission electron microscopy examination were used in vitro. RESULTS AND CONCLUSION： Both FA-CDDP-ASA-MNPs and CDDP could inhibit the growth of human laryngeal cancer Hep-2 cells, and there was no difference in their inhibitory rates（P〈0.05）. FA-CDDP-ASA-MNPs and CDDP showed increased inhibitory rates of human laryngeal cancer Hep-2 cells with the increase of CDPP concentration. The half maximal inhibitory concentrations of CDDP for inhibiting Hep-2 cells were significantly different at 24 and 48 hours after culture（P〈0.05）. Both FA-CDDP-ASA-MNPs and CDDP could cause apoptosis in Hep-2 cells, and the number of apoptotic cells was increased with the increase of drug concentrations（P〈0.05）, but there was no difference between two kinds of drugs（P〉0.05）. FA-CDDP-ASA-MNPs and CDDP at low concentrations could increase the percentage of cells at G0/G1, but decrease the cell proportion at S and G2/M phases（P〈0.05）. Under transmission electron microscope, Hep-2 cells with the intake of FA-CDDP-ASA-MNPs appeared to have notable apoptosis. These findings suggest that folic acid magnetic nanoparticles containing cisplatin can inhibit the growth of human laryngeal cancer Hep 2 cells, with no influence on the efficacy of cisplatin and with no cytotoxic effect.

关 键 词：生物相容性材料 组织工程 叶酸 生物材料 药物控释材料 磁性纳米颗粒 顺铂 化疗 喉癌 治疗 Hep-2细胞 毒性作用 凋亡 共培养 

分 类 号：R318[医药卫生—生物医学工程]