去甲斑蝥素N-乳糖酰壳聚糖纳米粒的肝靶向抗肿瘤药效学评价  

Study on an active hepatocyte-targeting antineoplastic activity of norcantharidin-loaded galactosylated chitosan nanoparticles

作　　者：胡玮[1] 章良[2] 王钦[1] 陈晓艳[1] 贝永燕[3] 许静玉[3] 王文娟[1] 张学农[1] 

机构地区：[1]苏州大学药学院药剂教研室,苏州215123 [2]苏州大学药学院生物制药教研室,苏州215123 [3]苏州大学药学院06级药学本科实习生,苏州215123

出　　处：《中国新药杂志》2010年第19期1814-1820,共7页Chinese Journal of New Drugs

基　　金：国家科技支撑计划项目(2006BAI09B00);国家科技部科技型中小企业技术创新基金(07C26223201333);国家大学生创新课题(57315924);江苏省“六大人才高峰”资助项目(2007094)

摘　　要：目的:考察去甲斑蝥素N-乳糖酰壳聚糖纳米粒的肝靶向抗肿瘤药效学。方法:离子诱导法制备去甲斑蝥素壳聚糖纳米粒(NCTD-CS-NPs)及去甲斑蝥素N-乳糖酰壳聚糖纳米粒(NCTD-GC-NPs);考察两种纳米粒在H22荷瘤小鼠体内的抗肿瘤活性,分别采用流式细胞仪检测及MTT法考察两种纳米粒对肝肿瘤细胞Bel-7402、肝正常细胞HL-7702的摄取和细胞毒性。结果:相同的流式测定条件下经乳糖酸修饰的纳米粒具有更强的平均荧光强度,表明其对两种细胞的亲和性更大。去甲斑蝥素(NCTD),NCTD-CS-NPs,NCTD-GC-NPs在Bel-7402中的IC50分别是(18.84±1.87),(16.38±1.48),(7.12±1.94)μg.mL-1,在HL-7702中的IC50分别是(22.66±1.74),(21.76±1.92),(12.79±1.71)μg.mL-1。2.0 mg.kg-1NCTD,NCTD-CS-NPs,NCTD-GC-NPs 3组对H22荷瘤小鼠的抑瘤率分别为28.97%,37.86%,43.56%,反映了纳米粒在H22荷瘤小鼠体内良好的肝靶向抗肿瘤活性。结论:去甲斑蝥素N-乳糖酰壳聚糖纳米粒发挥双重靶向作用,有望成为新型靶向抗肿瘤制剂。Objective：To investigate an active hepatocyte-targeting dosage form of norcantharidin-loaded galactosylated chitosan nanoparticles.Methods：Norcantharid-loaded galactosylated chitosan nanoparticles and chitosan nanoparticles were achieved by ionic cross-linkage process with galactosylated chitosan and chitosan as carrier materials.In vivo anti-tumor activity of nanoparticles was evaluated with mice bearing H22 liver tumor.In vitro cellular uptake and cytotoxicity of nanoparticles to Bel-7402 and HL-7702 were investigated with BD Facscalibur flow cytometry（Becton Dickinson,USA） and MTT assay.Results：Norcantharidin galactosylated chitosan nanoparticles（NCTD-GC-NPs） had better affinity with Bel-7402 and HL-7702 than norcantharidin chitosan nanoparticles（NCTD-CS-NPs）.The IC50 values of norcantharidin（NCTD）,NCTD-CS-NPs,NCTD-GC-NPs were（18.84±1.87）,（16.38±1.48）,（7.12±1.94） μg·mL-1 for Bel-7402,and were（22.66±1.74）,（21.76±1.92）,（12.79±1.71） μg·mL-1 for HL-7702.The inhibition ratios of 2.0 mg·kg-1 NCTD,NCTD-CS-NPs,NCTD-GC-NPs on mice bearing H22 liver tumor were 28.97%,37.86% and 43.56 %.NCTD-GC-NPs had stronger anti-tumor activity than NCTD and NCTD-CS-NPs.Conclusion：As dual hepatocyte-targeting carrier,galactosylated chitosan nanoparticles are expected to be a novel hepatocyte-targeting preparation.

关 键 词：去甲斑蝥素 N-乳糖酰壳聚糖 纳米粒 抑瘤 细胞摄入 细胞毒性 

分 类 号：R979.1[医药卫生—药品]