二硫键优化透明质酸介导的肝癌靶向纳米探针抗癌性及MR成像可行性的动物实验  

Preliminary study on animal experiment of disulfide-bonded hyaluronic acid-functionalized targeted sodium-meter probe for hepatocellular carcinoma

作　　者：刘国顺 杨惠康 李雯曦 熊炜烽 刘兆松 黎蕾[3] 郭媛 江新青 Liu Guoshun;Yang Huikang;Li Wenxi;Xiong Weifeng;Liu Zhaosong;Li Lei;Guo Yuan;Jiang Xinqing(Department of Radiology,Guangzhou First People′s Hospital,the Second Affiliated Hospital of South China University of Technology,Guangzhou 510180,China;Department of Geriatrics,Guangzhou First People′s Hospital,the Second Affiliated Hospital of South China University of Technology,Guangzhou 510180,China;Department of Radiology,the 184th Hospital of PLA,Yingtan 335000,China)

机构地区：[1]华南理工大学第二附属广州第一人民医院放射科,510180 [2]华南理工大学第二附属广州第一人民医院老年病科,510180 [3]解放军184医院放射科,江西省鹰潭市335000

出　　处：《中华放射学杂志》2019年第8期694-699,共6页Chinese Journal of Radiology

基　　金：国家自然科学基金会面上项目(81271665);广州市卫生计生科技一般引导项目(20181A011016);广州市卫生健康科技项目(20191A010006).

摘　　要：目的探讨二硫键优化透明质酸介导的肝癌靶向纳米探针在体内动物水平的抗癌性及MRI可行性。方法将21只皮下肝癌移植瘤裸鼠模型按数字表法随机分为对照组、透明质酸-聚己内酯@阿霉素/超顺磁性氧化铁(HA-PCL@DOX/SPIO)组、HA-二硫键-PCL@DOX/SPIO(HA-SS-PCL@DOX/SPIO)组,后2组为实验组,每组7只,实验组经尾静脉按Fe 5 mg/kg剂量注射探针,对照组经尾静脉注射同等量的生理盐水,于注射前及注射后不同时点(2、4、8 h)分别进行MRI扫描,测量肿瘤T2值,并计算T2值下降率。将21只原位肝癌移植瘤裸鼠模型按数字表法随机分成对照组、HA-PCL@DOX/SPIO组及HA-SS-PCL@DOX/SPIO组(实验组),每组7只,实验组连续3次间隔1 d经尾静脉按DOX 2 mg/kg注射药物探针,对照组经尾静脉注射同等量生理盐水,连续观察15 d,计算肿瘤的抑制率。采用单因素方差分析分析比较各组间计量资料的差异。结果HA-PCL@DOX/SPIO组和HA-SS-PCL@DOX/SPIO组各时间点T2值差异有统计学意义(P<0.05),其中注射后2、4、8 h的T2值均较平扫下降,差异有统计学意义(P<0.05);HA-SS-PCL@DOX/SPIO组的T2值下降率高于HA-PCL@DOX/SPIO组。HA-PCL@SPIO/DOX、HA-SS-PCL@DOX/SPIO组对肿瘤有明显的抑制作用,3组间瘤重的差异有统计学意义(F=21.513,P=0.000),其中HA-SS-PCL@DOX/SPIO纳米探针对肿瘤的抑制率(47.7%)明显高于HA-PCL@DOX/SPIO组(28.2%)。结论二硫键优化透明质酸介导的肝癌靶向纳米探针HA-SS-PCL@DOX/SPIO在体内动物水平具有高效抗癌性及MRI显像功能于一体,可在分子影像水平实现对肿瘤疗效的早期监测。Objective To preliminarily explore the anti-cancer efficiency of disulfide-bonded hyaluronic acid-functionalized targeted sodium-meter probe for hepatocellular carcinoma and the feasibility of MRI.Methods Twenty-one nude mice models of subcutaneous liver cancer transplantation were randomly divided into saline,hyaluronic acid-poly ε-caprolactone@doxorubicin/superparamagnetic iron oxide (HA-PCL@DOX/SPIO) and HA-disulfide-bonded-PCL@DOX/SPIO (HA-SS-PCL@DOX/SPIO) groups,with 7 mice in each group.The experimental groups were injected with micelles at a dose of Fe 5 mg/kg through the tail vein,and the control group was injected with the same amount of saline via the tail vein.MRI was performed before and after injection (2 h,4 h,8 h).The T2 value of the region of interest (tumor) was measured and its decline rate was calculated.Twenty-one nude mice models of orthotopic liver cancer transplantation were randomly divided into saline group,HA-PCL@DOX/SPIO and HA-SS-PCL@DOX/SPIO groups,with 7 mice in each group.The experimental groups were injected with micelles at a dose of DOX 2 mg/kg through the tail vein by three consecutive times a day apart,and the control group was injected with the same amount of saline through the tail vein.Continuous observation for 15 days to calculate tumor inhibition rate.One way ANOVA test was used.Results The T2 value of HA-SS-PCL@DOX/SPIO group decreased significantly after 2,4 and 8 hours (P<0.05) than initial time,which was distinct compared with HA-PCL@DOX/SPIO group.The growth rate of tumor in HA-SS-PCL@DOX/SPIO and HA-PCL@DOX/SPIO groups was significantly lower than that in the control group (F=21.513,P<0.05).The former had the most obvious inhibitory effect on orthotopic liver cancer (47.7% and 28.2%).Conclusion Disulfide-bonded hyaluronic acid-functionalized targeted sodium-meter probe for hepatocellular carcinoma (HA-SS-PCL@DOX/SPIO) has high anti-cancer efficiency and imaging function at the animal level in vivo,and can be used to monitor the early therapeutic effect of tumor at

关 键 词：磁共振成像 二硫键 透明质酸 纳米探针 

分 类 号：R445.2[医药卫生—影像医学与核医学] R735.7[医药卫生—诊断学]