文章摘要
王 玲,高 启,李 嘉,丁粉干,袁晨燕,张东生.C225偶联磁性白蛋白纳米球的制备、表征及联合磁流体热疗体外靶向抗肺癌的研究[J].南京医科大学学报,2018,(11):1487~1493,1505
C225偶联磁性白蛋白纳米球的制备、表征及联合磁流体热疗体外靶向抗肺癌的研究
Preparation and characterization of C225 conjugated magnetic albumin nanoparticles and targeted anti⁃lung cancer in vitro when combined magnetic fluid hyperthermia
投稿时间:2018-07-24  
DOI:10.7655/NYDXBNS20181101
中文关键词: 磁性纳米粒  白蛋白纳米球  西妥昔单抗(C225)  靶向  热疗
英文关键词: magnetic nanoparticles  albumin nanospheres  cetuximab(C225)  targeting  hyperthermia
基金项目:国家自然科学基金青年基金(81700678,81501525);江苏省南京市卫计委一般性课题(YKK16280)
作者单位
王 玲 东南大学附属中大医院超声诊断科江苏 南京 210009 
高 启 东南大学附属中大医院超声诊断科江苏 南京 210009 
李 嘉 东南大学附属中大医院超声诊断科江苏 南京 210009 
丁粉干 东南大学附属中大医院病理科江苏 南京 210009 
袁晨燕 东南大学附属中大医院检验科江苏 南京 210009 
张东生 东南大学医学院病理学与病理生理学系江苏 南京 210009 
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中文摘要:
      目的:制备抗表皮生长因子受体(epithelial growth factor receptor,EGFR)单抗西妥昔(C225)偶联的磁性白蛋白纳米球,对其表征并联合磁流体热疗观察其体外抑制肺癌细胞的效果。方法:化学共沉淀法制备Fe3O4磁性纳米粒,去溶剂化?交联法制备磁性白蛋白纳米球(magnetic albumin nanospheres,MANs),然后用双功能交联剂N?琥珀酰亚胺?3?(2?吡啶二硫代)丙酸酯[N?succinimidyl?3?(2?pyridyldithio)propionate,SPDP]将C225偶联其上制备C225?MANs。纳米球的形态、平均粒径、zeta电位、抗体结合率、含铁量、细胞靶向性及磁热动力学均被表征。最后采用CCK?8及流式细胞(flow cytometry,FCM)分析检测C225?MANs介导的体外双靶向磁流体热治疗肺腺癌细胞GLC?82的效果。结果:透射电镜显示制备的C225?MANs为球形,Fe3O4纳米粒被封装其内,Fe含量约2.0 mg/mL;平均水合粒径约为140 nm,带负电;在输出电流20 A、输出频率200 kHz的交变磁场作用下,不同Fe含量的C225?MANs能在 60 min内升温到39.3 ℃~52.0 ℃,且加热30 min后温度能保持恒定。FCM荧光检测显示抗体结合率为79.74%。免疫荧光实验和细胞MRI成像证实C225?MANs能够靶向GLC?82细胞。CCK?8与FCM分析显示双靶向联合治疗组的细胞增殖率明显低于其他治疗组,而凋亡率明显高于其他治疗组(P < 0.05)。结论:C225?MANs对肺腺癌细胞GLC?82具有良好的靶向效应,且双靶向磁流体热疗联合分子靶向治疗在体外能有效抑制肺癌细胞。
英文摘要:
      Objective:To prepare and characterize magnetic albumin nanospheres conjugated with cetuximab(C225),which is anti?epithelial growth factor receptor(EGFR) monoclonal antibody,as well as their in vitro anti?lung cancer effect when combined with magnetic fluid hyperthermia. Methods:Fe3O4 nanoparticles(NPs)were prepared by chemical co?precipitation,and magnetic albumin nanospheres(MANs) were prepare by desolvation?crosslinking method,then C225 was further conjugated to synthesize C225?MANs using N?succinimidyl?3?(2?pyridyldithio)propionate(SPDP). Their morphology,mean particle size,zeta potential,the antibody conjugation efficiency,iron content,specific cell?binding ability,and magnetothermal dynamic profiles were characterized. Lastly,the therapeutic effect of C225?MANs induced double targeted magnetic fluid hyperthermia on lung adenocarcinoma in vitro was evaluated using CCK?8 and flow cytometry(FCM)assay. Results:TEM micrographs showed that the prepared C225?MANs were approximately spherical. Fe3O4 NPs were well incorporated into the core of the nanospheres and the iron content was about 2.0 mg/mL. The mean hydrodynamic diameter was about 140 nm with negative charge. When placing in alternating magnetic field with the output frequency of 200 kHz and the output current of 20 A,the corresponding C225?MANs with different Fe concentrations could rise to a steady temperature ranging from 39.3 ℃ to 52.0 ℃,and the temperature could keep stable without any change after 30 min heating. The fluorescence percentage detected by FCM analysis revealed that the antibody conjugation efficiency was 79.74%. The ability of nanospheres targeting GLC?82 cells in vitro was confirmed by immunofluorescence experiments and magnetic resonance imaging. The proliferation rate of double C225 and magnetic?targeted combined group was significantly lower than any other therapy group(P<0.05),while the apoptotic rate of the double C225 and magnetic?targeted combined treatment group were significantly higher than any other therapy group(P < 0.05). Conclusion:C225?MANs had good targeting effect on GLC?82 cells at cellular level. Moreover,dual?targeted magnetic fluid hyperthermia combined with molecular targeted therapy can effectively combat lung cancer in vitro.
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