摘要目的 构建携带抗人表皮生长因子受体2(HER2)与阿霉素的靶向药物载体,并探讨具体外抗肿瘤效应.方法 以复乳法制备包载阿霉素的纳米粒,检测其外观形态、粒径分布、Zeta电位和体外释药情况.以耦联剂将阿霉素纳米粒与人源化抗HER2抗体Trastuzumab(Herceptin)耦联成免疫纳米粒,ELISA法检测其免疫活性,噻唑蓝法(MTT)检测其对高表达HER2的肿瘤细胞SKBR3的抗肿瘤效应.结果 构建的阿霉素纳米粒呈球形或类球形,平均粒径为( 198.2±12.4) nm,Zeta电位为-41mV,包封率为68.6％,体外96h药物释放量达50％.ELISA检测显示免疫纳米粒对肿瘤细胞SKBR3及SKOV3具有免疫活性,而对MCF-7几乎无免疫活性反应.SKBR3的细胞存活率比较显示,免疫纳米粒对细胞的抑制作用分别明显优于阿霉素纳米粒和阿霉素(均P＜0.05).结论 免疫纳米粒具有免疫性和靶向性,可有效抑制高表达特异抗原HER2肿瘤细胞的生长.

abstractsObjective To construct targeted drug carriers with anti-human epidermal growth factor receptor 2(anti-HER2) and doxorubicin,and to determine its anti-tumor effects in vitro.Methods Doxorubicin nanoparticles (DNPs) loaded with doxorubicin were prepared by using doable emulsion method,and their appearance,distribution characteristics of diameter,Zeta potential and in vitro drug release were asscsscd.Immunonanoparticles (INPs) were then formed by using coupling agents that combined DNPs with trastuzumab (Herceptin),the human anti-HER2 antibody.The immunologic activity was determined via enzyme-linked immunosorbent assay (ELISA),and anti-tumour effects on SKBR3,the tumor cells with intense HER2 expression,via MTT method.Results The constructed nanoparticles appeared spherical or para-spherical,with a mean diameter of ( 198.2± 12.4) nm,Zeta potential of-41 mV,encapsulation ratio of 68.6％ and 96-hour in vitro drug release of 50％,respectively.INPs were shown to be immunologically active to SKBR3 and SKOV3 tumor ceils,but not MCF-7,as indicated by ELISA.Additionally,comparison on SKBR3 snrvival rate suggested that INPs conferred remarkably higher tumor cell inhibitory effects than DNPs and doxorubicin (both P＜0.05 ).Conclusion The immunologic activity and targeting characteristics of IN Ps may result in effective inhibition of the growth of tumor cells with highly spccialized HER2 cxpression.