Herceptin介导的肿瘤靶向治疗用免疫磁性纳米微粒-南方医科大学学报.PDFVIP

2010;30(11 南方医科大学学报(JSouthMedUniv 窑2539 窑 Herceptin介导的肿瘤靶向治疗用免疫磁性纳米微粒的制备 李贵平袁黄 凯袁张 辉袁刘 峰袁陈旭坚渊南方医科大学南方医院核医学 袁广东 广州 510515冤 摘要院目的制备人源性单抗Herceptin介导的靶向HER-2/neu癌基因的免疫磁性纳米微粒遥 方法采用部分还原沉淀法 制备四氧化三铁磁微粒子袁并用硅烷偶联剂进行表面修饰袁利用戊二醛作为交联剂袁将单抗Herceptin 与磁性纳米微粒 进行交联构建免疫磁性纳米微粒遥 用扫描电镜(SEM 尧X-射线粉晶衍射(XRD 尧磁强计(VSM 尧X射线能谱仪(EDS 等分 析仪器对磁性纳米微粒的特性进行表征袁并对免疫磁性纳米微粒的免疫活性进行测定遥结果磁性纳米微粒经表面硅烷 修饰后平均粒径在20nm左右袁 磁饱和强度为65emu/g遥 磁性纳米微粒表面经氨基官能团化后袁 表面氨基密度为0.5 滋mol/mg袁 固载有组氨酸的磁性纳米微粒与人源性单抗Herceptin 偶联后平均粒径在 60nm 左右袁 且保持较好的 Herceptin 的免疫结合活性遥 结论通过化学偶联方法将针对HER-2/neu 癌基因的人源化单抗Heceptin 固定在磁性纳米 微粒的表面袁可满足进一步的肿瘤靶向治疗的要求遥 关键词院磁性纳米微粒曰表面修饰曰Herceptin曰靶向治疗 中图分类号院R73-362;R944 文献标识码院A 文章编号院1673-4254(2010)11-2539-04 Preparationofi unomagneticnanoparticlesfortumortargetingtherapywithherceptin LIGui-ping,HUANGKai,ZHANGHui,LIUFeng,CHENXu-jian DepartmentofNuclearMedicine,NanfangHospital,SouthernMedicalUniversity,Guangzhou510515,China Abstract: ObjectiveToprepareimmunomagneticnanoparticles (IMNs )forHER2/neu-targetedradioimmunotherapywith herceptin,ahumanizedanti-p185-HER-2/neumonoclonalantibodytargetingtheextracellulardomainofHER-2/neureceptor. Methods The magnetic nanoparticles were synthesized by partial reductive precipitation method and the surface of the particleswaschemicallymodifiedusingsilanecouplingagent. Herceptinandhistidinewerecovalentlylinkedtotheamine groupuponthesilica-coatedmagneticnanoparticlesmodifiedbyN- [3- (trimethyoxysilyl )propyl]-ethylenediamineusing glutaraldehydemethodtopreparetheIMNs. Thenanoparticleswereevaluatedbydiffraction (XRD), scanningelectron microscope(SEM)andX-rayenergyspectrometry(EDS), andtheimmunoreactivityofIMNwasdetermined. Results The averagediameterofthedecaniocacid-coatedFeO nanoparticlewasabout20nmwithamagneticsaturationof65emu/g.The 3 4 surface amino group was 0.5 滋mol/mg