125I-UdR壳聚糖纳米微粒对肝癌细胞的内照射生物学效应  

Biological effects of 125I-UdR chitosan nanoparticles on hepatoma cells

作　　者：杨辰[1] 朱然[2] 万建美[2] 周大勇[1] 宋妙丽[1] 高菲[1] 刘芬菊[2] 

机构地区：[1]南京医科大学附属苏州医院,苏州215000 [2]苏州大学放射医学与防护学院放射医学与防护重点实验室

出　　处：《中华放射医学与防护杂志》2015年第5期323-328,共6页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金（30870585,31270897,81302383）;江苏省重点高校学术发展计划（PAPD）

摘　　要：目的 评估125I-UdR壳聚糖载药纳米微粒（1255I-UdR-CS-DLN）对肝癌细胞的内照射生物学效应.方法 采用激光共聚焦显微镜观察125I-UdR-CS-DLN在肝癌细胞HepG2和人正常肝组织细胞HL-7702内的聚积和分布;通过MTT实验、流式细胞仪和单细胞凝胶电泳技术,评价内照射细胞生物学效应;采用TUNEL染色法观察兔肝原位肿瘤细胞经125I-UdR-CS-DLN靶向治疗后的细胞凋亡.结果 纳米微粒作用30 min后,其在HepG2细胞质内的聚积大于HL-7702;当125I-UdR-CS-DLN浓度大于37 kBq/ml时,HepG2细胞在纳米微粒作用后24、48 h的存活率显著低于HL-7702细胞（t=-4.46 ～6.31,P＜0.05）,且细胞周期G1期阻滞明显,G2/M期细胞明显受损;125I-UdR-CS-DLN造成细胞DNA双链断裂的程度明显高于125I-UdR,HepG2细胞的DNA损伤后修复能力显著低于HL-7702（Olive尾矩：t=2.94,P＜0.05;彗尾DNA％：t=10.64,P＜0.01）;兔肝原位癌模型经介入被动靶向治疗后的TUNEL染色结果表明,125I-UdR-CS-DLN可使兔肝原位肿瘤细胞产生明显的凋亡,而相同剂量125I-UdR作用后肿瘤并未出现明显的凋亡.结论 125I-UdR-CS-DLN进入肝癌细胞的能力明显强于125I-UdR,引起的DNA辐射损伤效应更强,可明显加剧肝癌细胞的凋亡,阻止DNA损伤修复.Objective To evaluate the internal irradiation biological effects of 125I-UdR chitosan nanoparticles in hepatoma cells.Methods The accumulation and distribution of 125I-UdR-CS-DLN in hepatoma cells HepG2 and human liver tissue cells HL-7702 were observed with a confocal microscopy.The internal irradiation biological effects were evaluated by MTT assay,flow cytometry and single cell gel electrophoresis.The apoptosis of in situ rabbit liver tumor treated with 125I-UdR-CS-DLN was assayed by TUNEL staining technique.Results After 30 min of nano-particle treatment,its accumulation in the cytoplasm of HepG2 cells was significantly greater than that in HL-7702 cells.When the concentrations of 125I-UdR-CS-DLN was higher than 37 kBq/ml,the cell viability of HepG2 was significantly lower than that of lL-7702 at 24 and 48 h post-treatment（t =-4.46-6.31,P〈0.05）,and the HepG2 cells were arrested at G1 phase and significantly impaired at G2/M phase.In addition,the degrees of DNA doublestrand break of both cell lines irradiated by 125I-UdR-CS-DLN were significantly higher than those treated with 125I-UdR,and the DNA repair capacity of HepG2 cells was significantly lower than that of HL-7702 cells（OTM：t =2.94,P 〈0.05;TDNA%：t =10.64,P 〈0.01）.TUNEL staining showed that cell apoptosis could be induced in the rabbit liver carcinoma by 125I-UdR-CS-DLN but not by 125I-UdR.Conclusions The amount of 125I-UdR-CS-DLN absorbed by hepatoma cells is significantly higher than that of 125I-UdR,which suggests that 125 I-UdR-CS-DLN induces more stronger internal radiation biological effects of apoptosis and DNA damage on hepatoma cells.

关 键 词：125I-UdR-壳聚糖-载药纳米微粒 肝癌 被动靶向 

分 类 号：R735.7[医药卫生—肿瘤]