环五肽RGD靶向的纳米金偶联VEGFsiRNA增强兔VX2肝肿瘤射频消融损伤效应的研究

发布时间：2018-08-08 17:23

【摘要】：目的:探讨环五肽RGD(Tyr RGD)靶向的纳米金颗粒(GNPs)偶联VEGF小干扰RNA(Tyr RGDGNPs-VEGFsi RNA)复合物对兔肝脏VX2肿瘤射频消融(RFA)损伤效应的影响。方法:采取开腹肝脏种植VX2肿瘤组织块的方法建立兔VX2肝癌模型。首先将6只肝癌兔均分为两组分别注射Tyr RGD-GNPs-VEGFsi RNA复合物和GNPs,注射48 h后,透射电镜检测两者在肿瘤标本中的聚集和分布情况。然后将30只肝癌兔均分为3组,分别注射Tyr RGD-GNPs-VEGFsi RNA复合物、GNPs、生理盐水48 h后,行RFA治疗,48 h后切取标本,行病理学观察,测量肿瘤毁损体积,TUNEL法检测残癌细胞凋亡。最后将27只肝癌兔均分为3组,分别行RFA+Tyr RGD-GNPsVEGFsi RNA注射,RFA+生理盐水注射、生理盐水注射,饲养至自然死亡,记录生存时间。结果:Tyr RGD-GNPs-VEGFsi RNA复合物在肿瘤中的聚集明显优于GNPs(14.2颗/500 nm视野vs.0颗/500 nm视野,P0.01)。注射Tyr RGD-GNPs-VEGFsi RNA复合物后的RFA治疗毁损体积明显大于注射GNPs和生理盐水(5.12 cm3 vs.1.78 cm3 vs.1.49 cm3,P0.01),且前者残癌区肿瘤细胞凋亡数明显高于后两者(111.7个vs.36.3个vs.34.7个,P0.01),而后两者上述指标差异均无无统计学意义(均P0.05)。RFA+Tyr RGD-GNPs-VEGFsi RNA治疗的肝癌兔较RFA+生理盐水治疗、单纯生理盐水治疗的肝癌兔的平均生存时间明显延长(70.9 d vs.51.2 d vs.43.9 d,P0.01)。结论:Tyr RGD-GNPs-VEGFsi RNA复合物能在肝脏肿瘤中靶向聚集,具有扩大RFA毁损范围和促进肿瘤细胞凋亡的作用,从而增强RFA疗效。
[Abstract]:Aim: to investigate the effect of RGD (Tyr RGD) targeting gold nanoparticles (GNPs) coupled with VEGF small interfering RNA (Tyr RGDGNPs-VEGFsi RNA (RNA (Tyr RGDGNPs-VEGFsi RNA) complexes on (RFA) damage in rabbit liver VX2 tumor after radiofrequency ablation. Methods: rabbit VX2 liver cancer model was established by open liver implantation of VX2 tumor tissue mass. At first, six rabbits were divided into two groups: Tyr RGD-GNPs-VEGFsi RNA complex and GNPs were injected respectively. After 48 h injection, the aggregation and distribution of Tyr RGD-GNPs-VEGFsi RNA complex and GNPs in tumor specimens were examined by transmission electron microscopy (TEM). Then 30 liver cancer rabbits were divided into three groups. After 48 hours of normal saline injection, the specimens were taken after RFA treatment, and the tumor damage volume was measured by Tunel method to detect the apoptosis of residual cancer cells. Finally, 27 liver cancer rabbits were divided into 3 groups. RFA Tyr RGD-GNPsVEGFsi RNA was injected with normal saline, fed to natural death, and survival time was recorded. Results the aggregation of the RGD-GNPs-VEGFsi RNA complex in tumor was significantly better than that in GNPs (14.2 / 500nm field vs.0 / 500nm field P0.01). The damage volume of RFA after injection of Tyr RGD-GNPs-VEGFsi RNA complex was significantly larger than that of GNPs and normal saline (5.12 cm3 vs.1.78 cm3 vs.1.49 cm ~ (3) P 0.01), and the apoptotic number of tumor cells in the former was significantly higher than that in the latter two (111.7 vs.36.3 vs.34.7 (P0.01), while the latter two were above mentioned indexes. There was no significant difference between the two groups (P0.05). RFA Tyr RGD-GNPs-VEGFsi RNA was more effective than RFA normal saline in the treatment of liver cancer in rabbits. The mean survival time of liver cancer rabbits treated with saline alone was significantly prolonged (70.9 d vs.51.2 d vs.43.9 D0.01). Conclusion the fraction Tyr RGD-GNPs-VEGFsi RNA complex can target aggregation in liver tumors, which can enlarge the range of RFA damage and promote the apoptosis of tumor cells, thus enhancing the curative effect of RFA.
【作者单位】：第三军医大学附属西南医院肝胆外科;
【基金】：国家自然科学基金资助项目(81272688) 重庆市应用开发(重点)基金资助项目(cstc2014yykf B10002)
【分类号】：R735.7

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