叶酸受体靶向相变造影剂增效高强度聚焦超声体内消融肿瘤的研究  

Efficacy enhancement of folate-receptor targeted phasetransition contrast agent for HIFU ablation of tumor in vivo

作　　者：周洋[1] 刘莹[1] 叶鸣[1] 王志刚[2] 周鸿[1] 

机构地区：[1]重庆医科大学附属成都第二临床学院成都市第三人民医院,成都610031 [2]重庆医科大学超声影像学研究所

出　　处：《中华超声影像学杂志》2017年第8期719-723,共5页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金青年基金项目（81401433）;四川省卫计委科研项目（130417）

摘　　要：目的研究叶酸受体靶向的相变纳米粒造影剂（FR-PNPCA）用于增效高强度聚焦超声（HIFU）体内消融肿瘤的价值。方法首先采用双步乳化法制备FR—PNPCA乳剂和非靶向的相变纳米粒乳剂（PNPCA）备用。然后选取建模成功的荷卵巢癌移植瘤裸鼠36只，随机等分为3组，用HIFU对肿瘤进行辐照。A组为对照组，即辐照前2h经尾静脉注射生理盐水；B组为非靶向组，在辐照前2h注射PNPCA；C组为靶向组，在辐照前2h注射FR—PNPCA。辐照过程中观察各组辐照区域视频灰度变化；1h后每组处死5只裸鼠取肿瘤行TTC染色，切片行HE染色观察肿瘤组织凝固性坏死情况；24h后处死剩余裸鼠，肿瘤切片作免疫组化PCNA和TUNEL观察治疗对肿瘤细胞增殖和凋亡的影响。结果A组辐照区域几乎未见到灰度变化，B组和C组均见到明显灰度变化，B、C组辐照后灰度变化面积和变化值与A组相比差异均有统计学意义（P〈0．05）；A组未见到明显的凝固性坏死，B组和C组肿瘤内均见到明显的凝固性坏死，且C组坏死的范围明显大于B组（P〈0．01）；B组和c组问细胞增殖率和凋亡率的差异均有统计学意义（P〈0．05）。结论叶酸受体靶向的相变超声造影剂不仅能显著增强HIFU消融肿瘤效果，而且能实时监控肿瘤的治疗过程，是一种有应用前景的HIFU增效剂。Objective To explore the value of Folate-receptor targeted phaseransition nanoparticle contrast agent （FR-PNPCA） in increasing efficacy of high intensity focused ultrasound （HIFU） ablation of xerograft tumor in vivo. Methods Firstly, the FR-PNPCA and non-targeted phasetransition nanoparticle contrast agent （PNPCA） were prepared by a two-step emulsification method respectively. Then 36 nude mice bearing xerograft ovary tumor were randomly divided into 3 groups and underwent HIFU ablation respectively. Group A was the control group, which was irradiated at 2 h after the injection of saline by the tail vein. Group B was the untargeted group, which was irradiated at 2 h after the injection of PNPCA. Group C was the targeted group, which was irradiated at 2 h after the injection of FR-PNPCA. The gray- scale changes of irradiating areas in tumors were observed during ablation. Some mice were sacrificed at 1 h after ablation and the tumors were resected to observe the coagulative necrosis by TTC staining and HE staining. Lastly, The remain mice were sacrificed at 24 h after ablation, and the tumor sections were analyzed with immunohistochemical method including PCNA and TUNEL to explore the effect of HIFU ablation on tumor cell proliferating and necrosis. Results Obvious gray-scale changes could be seen in all tumors in group B and C immediately after HIFU irradiation, but almost no changes were founded in group A. The differences of gray-scale change values and squares between group B and C were statistically significant （ P 〈0.05）. Coagulative necrosis with irregular shape and clear boundary was observed in group B and C after irradiation, and the range of necrosis in group C was much larger than that in group B （ P 〈 0.01）, but little necrosis was founded in group A. In addition, the differences of proliferating rate and necrosis rate between group B and C were statistically significant （ P 〈0.05）. Conclusions FR-PNPCA can not only significantly enhance the efficacy, but also can help mo

关 键 词：高强聚焦超声 微气泡 纳米技术 叶酸受体 

分 类 号：R454.3[医药卫生—治疗学] R730.5[医药卫生—临床医学]