^(131)I标记的肝癌核酸纳米火车的制备及生物分布研究  

Preparation and Biodistribution of^(131)I-labeled Hepatoma Nucleic Acid Nanotrain

作　　者：林雪 许杰华 段亚妮 朱雁秋 储圆圆 刘明明 覃杰[1] LIN Xue;XU Jie-hua;DUAN Ya-ni;ZHU Yan-qiu;CHU Yuan-yuan;LIU Ming-ming;QIN Jie(Department of Radiology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;De-partment of Nuclear Medicine,Zhuhai People′s Hospital,Zhuhai 519000,China)

机构地区：[1]中山大学附属第三医院放射科,广东广州510630 [2]珠海市人民医院核医学科,广东珠海519000

出　　处：《中山大学学报（医学科学版）》2023年第3期416-422,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(2018A030313200,2017A030313841);中山大学附属第三医院国自然基金培育项目(2021GZRPYMS06);中山大学附属第三医院“五个五”工程项目(2023WW605)。

摘　　要：【目的】构建^(131)I标记的肝癌核酸纳米火车(NT),并探讨其作为肝癌靶向新型核素载体的可能性。【方法】三条核酸短链经退火处理后自组装形成核酸长链并采用氯胺T法进行放射性碘标记得到^(131)I-NT,纸层析法测纳米粒子的标记率及放射化学纯度,检测标记产物在不同温度(4℃、室温)及不同的储存溶剂(PBS、纯血清)中的体外稳定性。通过激光共聚焦显微镜检测肝癌细胞对纳米粒子的特异性摄取情况,分别测定^(131)I-NT与人肝癌细胞HepG2、正常肝细胞L02结合后细胞的放射性摄取率。通过尾静脉注射^(131)I-NT至HepG2荷瘤小鼠体内,进行生物分布研究。【结果】^(131)I-NT标记率为(93.05±0.74)%,纯化后放化纯度为(98.35±0.32)%。4℃储存条件下,标记产物在PBS和纯血清中24 h后的放化纯度分别为(92.77±0.04)%、(89.43±0.2)%。^(131)I-NT分别与两种细胞孵育2 h后,HepG2细胞的放射性摄取率明显高于L02细胞。尾静脉注射^(131)I-NT后,荷瘤小鼠体内30 min、1 h、2 h肿瘤部位每克组织放射性摄取值分别为(4.90±0.55)%ID/g、(10.12±0.32)%ID/g、(4.25±0.31)%ID/g,T/M比值相应为7.33±2.04、36.54±12.72、44.93±7.90。【结论】成功构建了^(131)I标记的长链核酸纳米火车,具有较好体外稳定性,对HepG2细胞及HepG2细胞荷瘤小鼠模型具有较高的靶向性,显示^(131)I-NT可能是一种具有潜力的靶向人肝癌的核素载体,为肝癌靶向核素诊疗提供新思路。【Objective】To construct^(131)I-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma.【Methods】Three short nuc leic acid chains self-assembled to a long nucleic acid chain after being annealed,and^(131)I-NT was obtained by radioiodine labeling using chloramine T method.The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography.The stability of the labeled products in vitro at different temperatures and different storage solvents was detected.The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy,and the radioactive uptake ratio of^(131)I-NT combined with human hepatocellular carcinoma cell HepG 2 and normal hepatocyte L 02 was measured.The biodistribution of^(131)I-NT was obtained through injecting^(131)I-NT into HepG 2 tumor-bearing mice via tail vein.【Results】The labeling rate of^(131)I-NT was(93.05±0.74)%,and the radiochemical purity post purification was(98.35±0.32)%.Its radiochemical purity in PBS and pure serum at 4℃for 24 h was(92.77±0.04)%and(89.43±0.2)%,respectively.The radioactivity up-take rate of HepG 2 cells was higher than that of L 02 cells after^(131)I-NT was incubated with two kinds of cells for 2 h significantly.After injection of^(131)I-NT through tail vein,the radioactive uptake per gram of tumor tissue were(4.9±0.55)%ID/g,(10.12±0.32)%ID/g and(4.25±0.31)%ID/g at 30 min,1 h and 2 h,respectively.The T/M ratio was 7.33±2.04,36.54±12.72 and 44.93±7.90 respectively.【Conclusions】The^(131)I-labeled long chain nucleic acid nanotrain was constructed suc-cessfully,which possesses relatively high stability in vitro,and high targeting ability to HepG 2 cells in vitro and HepG 2 tumor-bearing mouse model.Our study demonstrated that^(131)I-NT may be a potential radionuclide carrier targeting human liver cancer,which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinom

关 键 词：肝癌 适配体 纳米火车 放射性碘标记 生物分布 

分 类 号：R817.1[医药卫生—影像医学与核医学]