抗EGFR单抗偶联吉西他滨聚氰基丙烯酸正丁酯纳米粒对胰腺癌的靶向治疗  

Targeted delivery of gemcitabine to pancreatic adenocarcinoma using antiEGFR antibody as a targeting agent

作　　者：李春梅[1,2] 张林[1] 侯艳红[1] 李楠[1] 车明环 

机构地区：[1]中国人民解放军第309医院消化科,北京市100091 [2]河北北方学院,河北省张家口市075000

出　　处：《世界华人消化杂志》2015年第12期1890-1896,共7页World Chinese Journal of Digestology

摘　　要：目的:制备表面偶联抗表皮生长因子受体(epidermal growth factor receptor,EGFR)单抗的聚氰基丙烯酸正丁酯纳米微球(EGFRgrafted polybutylcyanoacrylate nanoparticles,EGFR-PBCA-NP),研究负载吉西他滨(gemcitabine,GEM)的靶向纳米粒子对胰腺癌的治疗作用.方法:(1)采用乳化聚合法制备负载GEM的纳米微球,测定载药纳米粒的粒径、载药率、包封率;(2)建立裸鼠胰腺癌模型,随机分为5组,每组10只.每3 d尾静脉给药1次,治疗前测量肿瘤长径(a)和短径(b),计算肿瘤体积.治疗12 d停药后处死裸鼠剥离瘤体测量肿瘤大小,对瘤体进行称质量并计算抑瘤率;(3)随机将荷瘤小鼠分为两组,每组于给药后1、5、12 h处死,提取肿瘤组织用于冰冻切片荧光观察.结果:与对照组相比各实验组移植瘤的瘤质量抑制率和体积差异具有统计学意义(P<0.05),其中EGFR-GEM-PBCA-NP组显著优于其他各组.EGFR-Cy3-PBCA-NP组荧光强度于1、5、12 h均强于Cy3-PBCA-NP组,并且实验组于5 h时荧光强度强于1、12 h.结论:EGFR-GEM-PBCA-NP对EGFR阳性的裸鼠人胰腺癌移植瘤有明显的靶向性和显著的抑瘤作用.AIM： To investigate the capability of epidermal growth factor receptor （EGFR）-grafted polybutylcyanoacrylate nanoparticles （EGFR- PBCA-NP） carrying gemcitabine （GEM） to treat pancreatic cancer. METHODS： GEM nanoparticles were prepared by emulsion polymerization, and the particle size, drug-loading rate and encapsulation efficiency were characterized. Different numbers of PANC-1 cells in 100 μL PBS were inoculated subcutaneously into the right flank of Balb/c （nu/nu） mice to establish a xenograft model. The mice were divided into five groups （n = 10 each）. The drugs were injected through the mouse tail vein to observe tumor inhibition. Every three days the short diameter and long diameter of tumors were measured to calculate tumor volume. After 12 d, the mice were killed. Tumor weight and volume were measured in nude mice bearing xenografts to calculate the tumor inhibition rate. Xenograft nude mice were randomly divided into two groups. Tumor tissues were removed from the mice which were sacrificed at 1, 5, and 12 h after the injection for frozen section fluorescence examinations. RESULTS： As compared with the control group, the weight and volume of human pancreatic cancer xenografts of nude mice in the experimental group were decreased significantly （P 〈 0.05）. The two indexes in the EGFR-GEM-PBCA-NP group were significantly better than those in other groups. In the experimental group （EGFR-Cy3-PBCA- NP）, fluorescence intensity at 1, 5, and 12 h was stronger than that in the control group （Cy3-PBCA-NP）, and fluorescence intensity in the experimental group at 5 h was stronger than that at I and 12 h.CONCLUSION： EGFR-GEM-PBCA-NP shows a good receptor targeting ability and a significant inhibitory effect on human pancreatic cancer.

关 键 词：聚氰基丙烯酸正丁酯纳米粒 吉西他滨 表皮生长因子受体 胰腺癌 移植瘤 

分 类 号：R735.9[医药卫生—肿瘤]