超声可视可降解聚乳酸-羟基乙酸共聚物-Fe3O4原位植入物磁感应热消融裸鼠洲C-7721人肝癌  

Clinical effect of ultrasound-guided injection of biodegradable poly（lactic-co-glycolic acid）-F3O4 in situ implant for magnetic thermal ablation in treatment of nude mice with human liver cancer SMMC-7721 cells

作　　者：梁冰[1] 左国庆[3] 郑元义[2] 何松[1] 左的于[2] 

机构地区：[1]重庆医科大学附属第二医院消化内科,400010 [2]重庆医科大学,400016 [3]重庆市中医院,400021

出　　处：《中华肝脏病杂志》2016年第12期911-915,共5页Chinese Journal of Hepatology

基　　金：国家自然科学基金（81271598）

摘　　要：目的制备载Fe3O3可降解液固相变型聚乳酸-羟基乙酸共聚物（PLGA）原位植入物，在超声引导下注入裸鼠肿瘤模型内，观察其在交变磁场下对裸鼠SMMC-7721人肝癌的磁热治疗效果。方法制备含10％Fe3O4-PLGA原位植入物，取50μlFe3O4-PLGA—NO甲基吡咯烷酮（NMP）凝胶注入昆明小鼠皮下，并连续2个月观察材料的降解情况，同时记录昆明小鼠体质量变化。取注入材料昆明鼠的心、肝、脾、肺、肾组织行HE染色和普鲁士蓝染色。取离体牛肝，切成2cm×2cm×2cm立方体，注入50μlFe3O4-PLGA-NMP凝胶，待相变后，分别加热1、2、3、4、5min，剖开观察消融范围，行HE染色。在超声引导下向荷瘤裸鼠肿瘤内注入50μlFe3O4-PLGA—NMP材料后行微-CT检查，随后将裸鼠分为治疗组和对照组；治疗组磁热治疗3min，对照组不进行磁热治疗，治疗后每日观察肿瘤的生长情况。结果Fe3O4-PLGA—NMP植入物可降解性实验表明经皮下注射的材料2个月后经肝脾逐渐代谢消失，且昆明小鼠生命状态良好。牛肝消融实验观察到50μlFe3O4-PLGA植入物消融直径可达（1．46±0．11）cm，HE染色显示牛肝消融的部分发生凝固性坏死。Fe3O4-PLGA凝胶相变实验表明，材料注入肿瘤遇水后可迅速发生液固相变，可在超声和CT监测下显示相变过程。肿瘤消融后治疗组肿瘤大体形态显示，于治疗后第2天肿瘤开始脱落、结痂，15d后创面开始愈合，肿瘤组织完全消失；对照组肿瘤大小无变化。结论超声可视下可降解Fe3O4-PLGA原位植入物结合磁感应热消融技术能有效地消融裸鼠SMMC-7721人肝癌。Objective To prepare the Fe304-1oaded biodegradable liquid-solid phase inversion poly（lactic-co-glycolic acid） （PLGA） in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an altemating magnetic field. Methods An in situ implant containing 10% Fe3O4 was prepared, and 50 μl Fe3O4-PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 μl Fe3O4-PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 μl Fe3O4-PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results The biodegradation of Fe3O4-PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 μl Fe3O4- PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe3O4-PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid-solid phase inversion could be monitored by ultrasound and CT. The detachment and

关 键 词：癌 肝细胞  磁热治疗 植入物 可降解 超声可视 

分 类 号：R735.7[医药卫生—肿瘤]