阿霉素纳米-VEGFR2单抗交联物的抗肝癌作用  

The effect of adriamycin nanoparticles-VEGFR2 monoclonal antibody on hepatic carcinoma

作　　者：殷香保[1] 邬林泉[1] 黄长文[1] 黄明文[1] 罗志强[1] 周凡[1] 黄俊[1] 

机构地区：[1]南昌大学第二附属医院普外科,南昌330006

出　　处：《广东医学》2014年第19期2972-2975,共4页Guangdong Medical Journal

基　　金：国家自然科学基金项资助项目(编号:81060187);江西省自然科学基金资助项目(编号:2008GQY0050;20114BAB205017)

摘　　要：目的探讨阿霉素纳米-VEGFR2单抗交联物抗肝癌作用,研究其在体内对肝癌组织生长的抑制作用及其对肝癌祼鼠生存期的影响。方法 (1)选择10只肝癌裸鼠随机分为两组,按尾静脉注射不同成分分别为交联物A组和阿霉素溶液(F-ADM)组,使用高效液相色谱法测定交联物在肝癌裸鼠体内分布;(2)选择18只肝癌裸鼠随机分为3组,按尾静脉注射不同成分分别为交联物B组、F-ADM组及生理盐水(NS)组,每组在给药当天及给药后第3、6、9、12、15、18、21天分别用游标卡尺测量肿瘤并计算体积,给药后第21天处死全部裸鼠,称肿瘤质量。(3)选择30只肝癌裸鼠随机分为3组,按尾静脉注射不同成分分别为交联物C组、F-ADM组、NS组,观察并记录各组肝癌裸鼠的生存时间。结果注射交联物A组肝癌裸鼠2 h后的肿瘤、血液、心、肝、肾中的阿霉素浓度与注射阿霉素纳米裸鼠(纳米组)差异具显著统计学意义(P<0.05);给药2 h时药物的靶向指数及选择性指数以肿瘤最高;3组肿瘤体积均随着时间的延长逐渐增大,但交联物B组增长最慢,其肿瘤体积在给药后第9、12、15、18、21天均明显小于F-ADM组,肿瘤质量在给药后第21天明显轻于F-ADM组(P<0.05);交联物C组和F-ADM组裸鼠的存活率得到改善,从6周开始交联物C组裸鼠的存活率明显高于NS组,在9、10、11、12周交联物C组裸鼠的存活率明显高于F-ADM组(P<0.05)。结论阿霉素纳米-VEGFR2单抗交联物在抗肝癌过程中实现缓慢释放和靶向性作用,增加了药物在肝及肿瘤中的分布比例,延长了药物的作用时间,有助于提高肿瘤的治疗效果。Objective To investigate the protective effect of adriamycin nanoparticles - VEGFR2 monoclonal an- tibody against hepatic carcinoma via study its effects on liver cancer tissue growth inhibition and the survival of liver cancer nude mice. Methods Hepatocellular carcinoma （ HCC ） model nude mice were constructed. （ 1 ） 10 HCC nude mice were randomly divided into crosslinked product group （crosslinked A group） and F- ADM nanoparticles group （F -ADM group） according to different drugs injected into tail veins. Crosslinked product distribution was measured by HPLC. （2） 18 HCC nude mice were randomly divided into crosslinked product group （crosslinked B group）, F- ADM nanoparticles group （F -ADM group） and normal saline group （NS group） according to different drugs injected into tail veins. Tumor size was measured after injecting drug and on the 3^rd, 6^th, 9^th, 12^th, 15^th, 18^th and 21^st day. All mice were sacrificed on the 21^st day and the tumor weight was measured. （3） 30 HCC nude mice were randomly divided into crosshnked product group （crosslinked C group）, F- ADM nanoparticles group （F- ADM group） and normal saline group （NS group） ac- cording to different drugs injected into tail veins. Survival time were observed and recorded. Results There were signifi- cant differences in tumor, blood, heart, liver and kidney ADM concentrations between the crosslinked product groups and F - ADM nanoparticles group 2 hours after drug injection （ P 〈 0. 05 ）. Highest DTI and DSI were observed in tumor 2 hours after injection. Tumor volume and weight in all three groups gradually increased with time, however, the slowest growth was observed in crosslinked B group. The tumor volume in crosslinked B group was significantly smaller than F - ADM group on the 9^th, 12^th, 15^th, 18^th and 21^ st day, and also with significant lower tumor weight （ P 〈 0. 05 ）. Survival rate of crosslinked C group and F - ADM group was both improved, as the survival rate of crosslinked C

关 键 词：纳米微粒 VEGFR2单抗 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]