131^I标记纳米脂质体靶向治疗结肠癌的实验研究  

Evaluation of the internal therapeutic effectiveness of 131^I-antiEGFR-BSA-PCL in nude mice with colorectal cancer

作　　者：季艳会 李玮[1] 李承霞[1] 李宁[1] 常津[2] 谭建[1] 

机构地区：[1]天津医科大学总医院核医学科,300052 [2]天津大学,300072

出　　处：《中华放射医学与防护杂志》2016年第2期81-86,共6页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金，National Natural Science Foundation of China

摘　　要：目的 研究 131^I-antiEGFR-BSA-PCL对LS180细胞结肠癌裸鼠移植瘤内照射的治疗效果.方法 构建抗表皮生长因子受体（EGFR）标记的纳米脂质体及EGFR靶向性.通过荧光共聚焦显微镜、细胞摄碘实验观察纳米载体的靶向性及LS180细胞对其摄取情况.将裸鼠40只按随机数字表法分为4组,通过瘤体内注射的方式向移植瘤内分别注射74 MBq （740 MBq/ml）1 31I-antiEGFR-BSA-PCL、 131^I-BSA-PCL 、 131^I及相同体积的生理盐水.通过研究裸鼠体重、肿瘤体积、SPECT显像及组织病理学方法,观察纳米脂质体的抑瘤效果.结果 共聚焦实验显示,与BSA-PCL组相比,antiEGFR-BSA-PCL组细胞内绿色荧光较明显,其介导的胞吞效应显著.摄碘率实验中,LS180细胞对 131^I-antiEGFR-BSA-PCL的摄取率明显高于1 31I-BSA-PCL（t=2.77 ～ 5.40,P＜0.01）. 131^I-antiEGFR-BSA-PCL组与 131^I-BSA-PCL组裸鼠肿瘤增殖均较慢,二者差异无统计学意义（P＞0.05）.给药后72 h, 131^I-antiEGFR-BSA-PCL与 131^I-BSA-PCL的肿瘤摄取率分别为（21.61±1.01）和（20.58±0.65）％ID/g,均明显高于131I组（t=9.36、8.69,P＜0.01）. SPECT显像显示纳米脂质体主要特异性积聚在肿瘤区.结论 131I-antiEGFR-BSA-PCL对LS180结肠癌裸鼠移植瘤有明显的抑制作用.Objective To investigate the biological effects of internal radiation and therapeutic effectiveness of 131^I-labeled anti-epidermal growth factor receptor （EGFR） in colorectal cancer of model mice.Methods Nano-liposome characterized for EGFR-targeting was constructed.The efficacy of cellular binding and uptake of the liposome was evaluated by the analysis of confocal microscopy observation and the iodide uptake assay.After intra-tumor injections of 74 MBq （740 MBq/ml） 131 I-antiEGFR-BSA-PCL,131 I-BSA-PCL, 131^I or an equivalent volume of normal saline.The biological effects of internal irradiation and therapeutic efficacy of the liposomes on colorectal cancer modeled in a male BALB/c mouse were evaluated by means of tumor size,body weight,histopathology,and SPECT imaging.Results The confocal fluorescence images showed that the antiEGFR-BSA-PCL was successfully internalized into LS180 cells.The 131I uptake efficacy of 131I-antiEGFR-BSA-PCL was significantly higher than that of 131I-BSA-PCL in LS180 cells （t =2.77-5.40,P 〈 0.01）.Tumor size measurement showed that tumor growth was inhibited by the treatment with 131 I-EGFR-BSA-PCL and 131I-BSA-PCL,but had no significant differences between these two groups （P 〉0.05）.It was found that the 131I-antiEGFR-BSA-PCL was markedly taken up by the tumor and reac hed its uptake value of （21.61 ±1.0 1） and （20.58 ± 0.65）% ID/g at 72 h following drug injection,which was higher than the uptake value of 131 ^I （t =9.36,8.69,P 〈 0.01）.SPECT imaging assay showed that,after being injected into mouse tumor,the 131^ I-EGFR-BSA-PCL and 131I-BSA-PCL were uniformly distributed inside the tumor.Conclusions 131 I-antiEGFR-BSA-PCL obviously suppresses the development of colorectal cancer in mice.

关 键 词：结肠癌 纳米脂质体 表皮生长因子受体 

分 类 号：R817.5[医药卫生—影像医学与核医学] R735.35[医药卫生—放射医学]