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超声引导注射可生物降解聚乳酸-乙醇酸共聚物-FeO原位植入物用于磁热消融治疗人肝癌SMMC-7721细胞裸鼠的临床效果

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

作者信息

Liang B, Zuo G Q, Zheng Y Y, He S, Zuo D Y

机构信息

Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2016 Dec 20;24(12):911-915. doi: 10.3760/cma.j.issn.1007-3418.2016.12.007.

Abstract

To prepare the FeO-loaded 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 alternating magnetic field. An in situ implant containing 10% FeO was prepared, and 50 μl FeO-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 FeO-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 FeO-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. The biodegradation of FeO-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 FeO-PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of FeO-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 incrustation of the tumor started at 2 days after treatment, the wound started to heal 15 days later, and the tumor tissue disappeared completely. Ultrasound-guided injection of biodegradable FeO-PLGA in situ implant combined with magnetic thermal ablation can effectively treat human liver cancer SMMC-7721 cells in nude mice.

摘要

制备负载FeO的可生物降解液-固相转变聚乳酸-羟基乙酸共聚物(PLGA)原位植入物,用于超声引导下注射到裸鼠肿瘤模型中,并研究其在交变磁场中对荷人肝癌SMMC-7721细胞裸鼠进行热磁治疗的临床效果。制备含10%FeO的原位植入物,将50μl FeO-PLGA-NMP凝胶注射到昆明小鼠皮下组织。连续2个月观察该材料的降解情况,并记录体重变化。对昆明小鼠的心、肝、脾、肺、肾进行苏木精-伊红(HE)染色和普鲁士蓝染色。取新鲜离体牛肝,切成2cm×2cm×2cm的立方体,然后注射50μl FeO-PLGA-NMP凝胶;相转变后,分别对离体牛肝立方体加热1、2、3、4和5分钟,然后切开观察消融范围;同时进行HE染色。在超声引导下将50μl FeO-PLGA凝胶注射到裸鼠肿瘤内后进行微型计算机断层扫描(Micro-CT),然后将裸鼠分为治疗组和对照组。治疗组小鼠接受3分钟热磁治疗,每天观察肿瘤生长情况。FeO-PLGA-NMP植入物的生物降解表明,皮下注射的材料在注射后2周逐渐代谢,裸鼠状态良好。牛肝消融实验表明,50μl FeO-PLGA植入物的消融范围达到1.46±0.11cm。HE染色显示部分牛肝有凝固性坏死。FeO-PLGA凝胶的相转变实验表明,材料注射到肿瘤内后迅速发生液-固相转变,且液-固相转变过程可通过超声和CT监测。治疗后2天肿瘤开始脱落结痂,15天后伤口开始愈合,肿瘤组织完全消失。超声引导下注射可生物降解的FeO-PLGA原位植入物联合磁热消融可有效治疗裸鼠体内的人肝癌SMMC-7721细胞。

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