新型NGR靶向载shRNA脂质微球抑制胶质瘤的生长

赵贯建; 张翔; 程远; 王志刚; 黄琴

doi:10.3971/j.issn.1000-8578.2019.18.1990

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

摘要

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-lipo-NGR），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。

Abstract:
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 12th, 17th and 22th day(P < 0.05). The median survival times of the shBirc5-lipo-NGR, shBirc5-lipo, shControl-lipo-NGR 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.

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