靶向HER-2多模态纳米探针的制备及性能研究  

Preparation and characterization of HER2-targeted multimodal nanoprobes

作　　者：安改丽[1] 刘屹[1] 喻凤[1] 陈小龙[2] 郭维[3] AN Gaili;LIU Yi;YU Feng;CHENG Xiaolong;GUO Wei(Department of Medical Oncology,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Imaging,Shaanxi Provincial People’s Hospital;Department of Education Administration,Shaanxi Provincial People’s Hospital)

机构地区：[1]陕西省人民医院肿瘤内科,西安710068 [2]陕西省人民医院影像科 [3]陕西省人民医院教学科

出　　处：《山西医科大学学报》2020年第5期382-387,共6页Journal of Shanxi Medical University

基　　金：陕西省自然科学基金基础研究面上项目(2017JM8106)。

摘　　要：目的探讨多模态靶向HER-2探针的合成方法及其对乳腺癌细胞体外靶向结合的可行性与在荷瘤小鼠体内生物分布情况。方法合成超顺磁性氧化铁纳米颗粒SPIO-PAA和靶向HER-2的多模态纳米探针SPIO-herceptin-NOTA-AI^18F,通过电子显微镜观察、动态光散射仪器检测、磁性分析、脂水分配系数测定和体外稳定性试验对其理化性能进行评估。MTT法检测对细胞增殖的影响;体外细胞特异性结合实验确定纳米探针的靶向活性,分析其在荷瘤小鼠体内的分布和代谢。结果透射电镜下SPIO-PAA形状规则,具有良好的分散性和均匀的粒径。SPIO-herceptin-NOTA-AI^18F的饱和磁化强度为50.38 emu/g,具有明显的亲水性。动物模型显示该探针主要分布于肿瘤组织、血液、肝脏、脾脏和肾脏,主要由肝脏代谢,肾脏排泄。结论SPIO-herceptin-NOTA-AI^18F具有良好的理化性能和体外生物学特性,符合MRI和PET检查的要求,且靶向性强,生物安全性好,具有临床应用潜能。Objective To investigate the synthesis of HER-2-targeted multimodal nanoprobes,and explore the feasibility of its binding with breast cancer cells in vitro and its biological distribution in tumor-bearing mice.Methods The superparamagnetic iron oxide nanoparticles(SPIO-PAA)and multimodal nanoprobe SPIO-herceptin-NOTA-AI^18F were prepared,and the electronic microscope,the dynamic light scattering instrument testing,the magnetic analysis,the determination of fat water distribution coefficient and the stability test in vitro were used to evaluate the physical and chemical properties.The effect of nanoprobe on cell proliferation was detected by MTT assay.The targeting activity of the nanoprobe was determined by cell specific binding experiments in vitro,and the distribution of SPIO-herceptin-NOTA-AI^18F in tumor-bearing mice was analyzed.Results TEM showed that the SPIO-PAA nanoparticles were of regular and spherical shape.The saturation magnetization of SPIO-herceptin-NOTA-AI^18F was 50.38 emu/g.The nanoprobe had obvious hydrophilicity.In vivo experiment showed that the nanoprobes were mainly distributed in tumor tissue,blood,liver,spleen and kidney,and were mainly metabolized by the liver and excreted by the kidney.Conclusion SPIO-herceptin-NOTA-AI^18F has good physical and chemical properties which meets the requirements of MRI and PET examination.It can specifically bind to HER-2 positive breast cancer cells in vitro,implicating good biological safety and clinical application potential.

关 键 词：分子成像 纳米粒子探针 HER-2阳性乳腺癌 MRI PET-CT 

分 类 号：R319[医药卫生—基础医学]