新型NGR靶向载shRNA脂质微球抑制胶质瘤的生长  

New NGR-targeted shRNA-loaded Liposome Suppresses Glioma Growth

作　　者：赵贯建 张翔[1] 程远[1] 王志刚[2] 黄琴[1] ZHAO Guanjian;ZHANG Xiang;CHENG Yuan;WANG Zhigang;HUANG Qin(Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China;Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China)

机构地区：[1]重庆医科大学附属第二医院神经外科,重庆400010 [2]重庆医科大学附属第二医院超声影像研究所,重庆400010

出　　处：《肿瘤防治研究》2019年第8期677-682,共6页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金（81401505）

摘　　要：目的制备一种新型的NGR靶向载shRNA脂质体,研究其对大鼠原位胶质瘤的抑制作用。方法(1)先后制备脂质微球(lipo)、NGR靶向微球(lipo-NGR)和含质粒靶向微球(shBirc5-lipoNGR),并对各种微球的性质进行表征;(2)免疫组织化学法研究shBirc5-lipo-NGR对大鼠原位胶质瘤模型的靶向性;(3)MRI T2实时监测原位胶质瘤生长情况及观察大鼠生存期。结果(1)成功制备了新型脂质体shBirc5-lipo-NGR,其粒径和电位分别为(186.2±74.07)nm和(10.9±3.76)mV;(2)shBirc5-lipo-NGR组Birc5蛋白较shBirc5-lipo、shControl-lipo-NGR及对照组明显减少;(3)MRI T2显示在成瘤后的第12、17和22天时,对照组肿瘤的平均体积及生长速度是shBirc5-lipo-NGR组的4.7倍左右(P<0.05)。shBirc5-lipo-NGR、shBirc5-lipo、shControl-lipo-NGR及对照组的中位生存期分别为30、24、22和21天。结论成功制备了新型NGR靶向载shRNA脂质体,将其应用于治疗SD大鼠原位胶质瘤,显示出了明显的肿瘤靶向性,同时具有抑制肿瘤生长、延长大鼠生存期的作用。Objective To prepare the new NGR-targeted shRNA-loaded liposome, and investigate its suppressing effect on orthotopic C6 glioma in rats. Methods(1) Liposome(lipo), the NGR-targeted liposome(lipo-NGR) and shBirc5-loaded lipo-NGR were prepared successively, and all kinds of products were characterized accordingly;(2) The targeting property of shBirc5-lipo-NGR was researched by immunohistochemical method in orthotopic C6 glioma rats model;(3) The tumor growth in treated rats was monitored longitudinally with MRI T2, and the survival time of each rat was recorded simultaneously. Results(1) We successfully prepared shBirc5-lipo-NGR whose size and zeta potential were(186.2±74.07)nm and(10.9±3.76)mV;(2) The Birc5 protein was significantly decreased in shBirc5-lipo-NGR group, compared with shBirc5-lipo group, shControl-lipo-NGR group and control group;(3) The control group exhibited an average tumor volume and growth rate 4.7 times greater than that in the shBirc5-lipo-NGR group on the 12 th, 17 th and 22 th day(P<0.05). The median survival times of the shBirc5-lipo-NGR, shBirc5-lipo, shControl-lipoNGR and control groups were 30, 24, 22, 21 days, respectively. Conclusion We successfully prepare the new NGR-targeted shRNA-loaded liposome, and demonstrate its targeting property, obvious inhibitory effect on tumor growth and extending the survival time of orthotopic C6 glioma-bearing rats.

关 键 词：靶向脂质微球 胶质瘤 基因治疗 NGR 

分 类 号：R319[医药卫生—基础医学] R739.4