ARFI破坏微泡增强Fe_3O_4纳米粒子在大鼠皮下移植瘤靶向递送的实验研究  

ARFI microbubble destruction improves targeted delivery of Fe_3O_4 nanoparticles to subcutaneous transplantation tumor in SD rats

作　　者：刘思思[1] 丁俊[1] 李锐[1] 陈朝晖[1] 

机构地区：[1]第三军医大学西南医院超声科,重庆400038

出　　处：《第三军医大学学报》2015年第12期1226-1231,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81171359)~~

摘　　要：目的制备一种具有磁共振显像功能的Fe3O4纳米粒子,通过声脉冲辐射成像（acoustic radiation force impulse,ARFI）辐照脂质微泡（microbubbles,MBs）,探讨ARFI辐照微泡对Fe3O4纳米粒子在肿瘤组织分布的影响。方法采用高温水热法制备Fe3O4纳米粒子,检测其形态、大小、分布等,观察其体外磁共振显像效果。选取60只SD雌性大鼠,体质量为170~200 g,制备Walker256皮下移植瘤模型,分为6组（n=10）：单纯ARFI辐照组、单纯MBs组、ARFI辐照MBs组、单纯Fe3O4纳米粒子组、ARFI辐照Fe3O4纳米粒子组、ARFI辐照MBs和Fe3O4纳米粒子组。微泡0.2 m L及5 mg/kg Fe3O4纳米粒子经大鼠尾静脉推注,ARFI辐照条件为探头间隔5 s辐照肿瘤部位,累计辐照5 min。将处理后的SD大鼠肿瘤部位行MRI扫描观察肿瘤组织信号变化;处死SD大鼠,取组织标本行病理学分析。结果制备的Fe3O4纳米粒子形态规则,粒径分布均匀,具有磁共振显像功能。SD大鼠肿瘤组织普鲁士蓝染色结果为单纯Fe3O4纳米粒子组、ARFI辐照Fe3O4纳米粒子组、ARFI辐照MBs和Fe3O4纳米粒子组均可见点状蓝染颗粒。其中ARFI辐照MBs和Fe3O4纳米粒子组蓝染颗粒计数明显多于其余2组（P〈0.05）。SD大鼠肿瘤部位磁共振成像结果为单纯Fe3O4纳米粒子组、ARFI辐照Fe3O4纳米粒子组、ARFI辐照MBs和Fe3O4纳米粒子组经相应处理后T2＊WI均可见肿瘤内部低信号部分增加。结论 ARFI辐照MBs能够有效地提高Fe3O4纳米粒子在SD大鼠皮下移植瘤组织的分布,增强Fe3O4纳米粒子在活体肿瘤内的靶向递送效果。Objective To prepare Fe3O4 nanoparticles and explore their in vitro magnetic resonance（ MRI） effect,and investigate the impact of acoustic radiation force impulse（ ARFI） microbubble（ MB）destruction on targeted delivery of Fe3O4 nanoparticles to subcutaneous transplantation tumor in SD rats.Methods High-temperature hydrothermal reaction was used to prepare Fe3O4 nanoparticles,and the particle morphology,size,and distribution were assessed. Fe3O4 nanoparticles were applied to perform MRI in vitro.Sixty female SD rats（ 170- 200 g） were prepared to establish the subcutaneous transplantation tumor using Walker256 cells,and the rats were randomly divided into 6 groups（ n = 10）,which were treated by ARFI irradiation,MB injection,ARFI MB destruction,Fe3O4 nanoparticle injection,Fe3O4 nanoparticle injection and ARFI irradiation,and Fe3O4 nanoparticle injection and ARFI MB destruction,respectively. MBs and Fe3O4 nanoparticles were given by intravenous injection. The dose of MBs was 0. 2 m L per rat,and the dose of Fe3O4 nanoparticles was 5 mg / kg. ARFI irradiation parameters were exposure duration 5 s,then pause 5 s,and total 5 min. MRI was employed to observe the signal change of tumor before and after Fe3O4 nanoparticle injection and AFRI irradiation by T2＊-weighted imaging（ T2＊ WI）. The rats were killed for pathological assay after management. Results The prepared Fe3O4 nanoparticles were observed with regular spherical morphology and narrow size distribution, and had significant superparamagnetic properties for imaging.Prussian blue staining represented the distribution of Fe3O4 nanoparticles in the tumor. The Fe3O4 nanoparticle injection group,Fe3O4 nanoparticle injection and ARFI irradiation group,and Fe3O4 nanoparticle injection and ARFI MB destruction group were observed with blue stained particles,and the blue stained particles in the Fe3O4 nanoparticle injection and ARFI MB destruction group were statistically more than those in the other 2groups（ P 〈 0. 05）. Increased hypointen

关 键 词：ARFI成像 磁共振成像 靶向递送 纳米粒子 

分 类 号：R73-354[医药卫生—肿瘤] R730.41[医药卫生—临床医学]