Trastuzumab修饰四代聚酰胺-胺型枝状聚合物纳米粒靶向结肠癌细胞SW480的研究  

Trastuzumab enhances PAMAM nanoparticles targeting to colon carcinoma cell SW480

作　　者：罗芳[1] 胡铁辉[1] 

机构地区：[1]中南大学生物医学工程研究院卫生部肝胆肠外科研究中心,湖南长沙410008

出　　处：《中国现代医学杂志》2013年第11期40-45,共6页China Journal of Modern Medicine

摘　　要：目的该研究旨在探讨Trastuzumab修饰四代聚酰胺-胺型枝状聚合物纳米粒对结肠癌SW480的靶向效果,为构建新型的靶向结肠癌的纳米递送系统提供实验数据。方法 MTT法确定SW480细胞摄取PAMAM NPs和PAMAM-Trastuzumab NPs适当的浓度;通过激光共聚焦和荧光显微镜定性观察SW480对罗丹明B标记的PAMAM NPs和PAMAM-Trastuzumab NPs的摄取;并采用流式细胞计数仪定量研究SW480细胞对两者的摄取差别;尾静脉注射荷SW480瘤裸鼠研究两者体内分布情况。结果 PAMAM NPs和PAMAM-Trastuzumab NPs的浓度在0.2 mg/mL时细胞存活率较高且对SW480细胞的毒性较小。激光共聚焦断层扫描显示SW480细胞可以较好地摄取PAMAM-Trastuzumab NPs,同时流式细胞仪定量显示PAMAM-TrastuzumabNPs在SW480细胞的分布较PAMAM NPs高40%(P<0.05)。PAMAM NPs和PAMAM-Trastuzumab NPs在移植瘤中的分布明显多于其他脏器,并且随时间的延长PAMAM-Trastuzumab NPs体现了更好的靶向效果。结论体外与体内实验证明Trastuzumab修饰的PAMAM NPs对结肠癌细胞SW480有很好的靶向效果,可为结肠癌的靶向治疗提供较好的药物载体。【Objective】 PAMAM coupled with Trastuzumab nanoparticles（NPs） are used as a novel drug carrier to colon carcinoma cell SW480.This paper examined its effect on targeting SW480 cells.【Methods】 Cytotoxicities of PAMAM NPs and PAMAM-Trastuzumab NPs were assayed based on viability of SW480 cells measured by MTT method.The distribution of PAMAM NPs or PAMAM-Trastuzumab NPs labeled by Rhodmaine B（RB） in SW480 cells was observed with confocal laser scanning microscope（CLSM） or fluorescence microscope.Quantitative comparisons were made between cellular uptake of RB-loaded PAMAM or PAMAMTrastuzumab NPs by flow cytometer（FCM）.Finally,nude mice bearing colon carcinoma were adopted to investigate the distribution of PAMAM NPs or PAMAM-Trastuzumab NPs in different organs and cancer.【Results】 PAMAM NPs and PAMAM-Trastuzumab NPs did not show much cytotoxicity at the concentration of 0 ~0.2 mg/mL.PAMAM-Trastuzumab NPs were well uptaken after being incubated with SW480 cells for 3 h.Besides,Z-section and measurement with CLSM clearly showed that PAMAM-Trastuzumab NPs were well distributed.After the same co-incubation time,SW480 cells uptook much more PAMAM-Trastuzumab NPs than PAMAM NPs（P 0.05）.At 4~48 h after PAMAM NPs and PAMAM-Trastuzumab NPs were respectively injected via tail vein of nude mice,PAMAM NPs and PAMAM-Trastuzumab NPs were mainly distributed in cancers and colon compared to other organs.However,PAMAM-Trastuzumab NPs demonstrated better cancer targeting than that of PAMAM NPs.【Conclusion】 Compared with PAMAM,Trastuzumab grafted PAMAM showed better targeting ability to SW480 cells.Trastuzumab promotes SW480 cells＇ uptaking of PAMAM NPs and enhances the targeting efficiency,which makes PAMAM-Trastuzumab NPs a potential nano-carrier for drugs to liver cancers.

关 键 词：TRASTUZUMAB 四代聚酰胺-胺型枝状聚合物 纳米粒 靶向 结肠癌细胞SW480 

分 类 号：R735.35[医药卫生—肿瘤]