表阿霉素免疫纳米微粒靶向抗肝癌作用的研究  

Study of the targeting anti -hepatocarcinoma effect of anti -vascular endothelial growth factor receptor 2 McAb epirubicin loaded nanoparticles

作　　者：杨峰[1] 黄国祥[1] 袁淑仪[1] 庞泓[1] 王金林[1] 龚时文[1] 

机构地区：[1]广东省东莞市人民医院,广东东莞523126

出　　处：《中国医药导报》2013年第21期21-23,共3页China Medical Herald

基　　金：广东省东莞市医疗卫生科技计划一般项目(编号201210515001108)

摘　　要：目的制备表阿霉素(E-ADM)免疫纳米微粒(NPs),观察其对荷人肝癌裸鼠模型的靶向治疗效应。方法利用聚电解质复合法合成载表阿霉素纳米微粒(E-ADM-NPs),化学交联法合成载表阿霉素的抗血管内皮生长因子受体2(VEGFR2)单克隆抗体纳米微粒(E-ADM-Ab-NPs),观察E-ADM-Ab-NPs在荷人肝癌裸鼠模型体内的分布特点,观察药物的靶向抗肿瘤效应及其毒副作用。结果 E-ADM-Ab-NPs保留了抗VEGFR2单克隆抗体的活性;E-ADM-Ab-NPs组肿瘤组织中的E-ADM浓度为(31.85±4.78)mg/kg,显著高于E-ADM-NPs组(P<0.05);E-ADM-Ab-NPs组的瘤体积抑制率及瘤重抑制率为60.69%和58.54%,较E-ADM-NPs组和E-ADM原药组均明显增强(P<0.05);且E-ADM-Ab-NPs组的血白细胞计数、谷丙转氨酶及肌酐水平与空白对照组相比,差异均无统计学意义(P>0.05);而E-ADM原药组的血白细胞计数较空白对照组下降42.68%,血清谷丙转氨酶水平则升高88.06%(P<0.05)。结论 E-ADM-Ab-NPs具有免疫活性,其在动物模型体内呈导向性分布,可提高E-ADM的疗效并有效降低E-ADM的毒副作用,是一种安全的新型药物纳米靶向制剂。Objective To prepare anti-vascular endothelial growth factor receptor 2 （VEGFR2） McAb epirubicin （E- ADM） loaded nanoparticles （NPs） and explore its targeting anti-hepatocarcinoma effect. Methods Epirubiein loaded nanoparticles （E-ADM-NPs） were prepared by polyeleetrolyte complexation and E-ADM-Ab-NPs were made by chemical crosslinking methods. Distribution property of E-ADM-Ab-NPs in nude mice bearing human hepatocarcino- ma were explored. Targeting anti-tumor effect of E-ADM-Ab-NPs and side effects concerned were observed. Results The immunoreactivity of E-ADM-Ab-NPs was well preserved. Concentration of E-ADM in tumor tissues in E-ADM- Ab-NPs group was （31.85~4.78） mg/kg, which was far higher than that of E-ADM-NPs group （P 〈 0.05）. The inhibi- tion rates of volume of tumor and weight of tumor in E-ADM-Ab-NPs group were 60.69% and 58.54%, which were significantly higher than that of E-ADM-NPs group and E-ADM group （P 〈 0.05）, and there were no significant dif- ferences between E-ADM-Ab-NPs group and control group in WBC count, sernm alanine transferase level or creati- nine level （P 〉 0.05）. Compared with control group, the E-ADM group decreased by 42.68% in WBC count, and in- creased by 88.06% in alanine transferase （P 〈 0.05）. Conclusion E-ADM-Ab-NPs has immunoreactivity and its dis- tribution in nude mice bearing human hepatocarcinoma is targeting. E-ADM-Ab-NPs can enhance therapeutic effect of E-ADM with less side effects, which indicate its potential as a novel, safe nano-tumor-targeting drug.

关 键 词：表阿霉素 聚电解质复合法 载药纳米微粒 肝癌 血管内皮生长因子 靶向给药 

分 类 号：R735.9[医药卫生—肿瘤]