基础研究(Basic Research)

载VEGF siRNA 环五肽RGD 偶联纳米金颗粒的基本特性及在射频消融中的应用

Published at: 2015年第24卷第1期

熊青 1 , 邹孟达 1 , 邓青松 1 , 李晓武 1 , 马宽生 1 , 别平 1
1 第三军医大学附属西南医院 肝胆外科,重庆 400038
通讯作者 宽生 马 Email: makuansheng@vip.sina.com
DOI: 10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2015.01.009
基金:
国家自然科学基金资助项目 81272688

摘要

目的:探讨VEGF siRNA 环五肽RGD 偶联纳米金颗粒(GNP)复合物(GNP-TyrRGD-VEGFsiRNA) 的基本特性,以及对肝脏射频消融(RFA)毁损效应的影响。 方法:利用化学和静电吸附的方法合成GNP-TyrRGD-VEGFsiRNA;电镜观察复合物的离散性;凝胶电泳 检测复合物中VEGF siRNA 的稳定性;采用CCK-8 法检测复合物对正常肝细胞的细胞毒性;电镜检测复 合物与正常肝细胞、肝癌细胞共孵育后的结合能力;在离体猪肝上检测复合物对RFA 毁损效果的影响。 结果:复合物较单纯GNP 有更好的离散性;复合物所含VEGF siRNA 量基本等于最初VEGF siRNA 加入量;复合物与单纯GNP 在30% 的浓度以下均对正常肝细胞几乎无毒性;复合物对肝癌细胞的结合 力明显高于正常肝细胞(P<0.05),而单纯GNP 对两种细胞的结合力无明显差异(P>0.05);经射频针 注入复合物的射频毁损直径明显大于注入生理盐水的对照组[(2.19±0.24)cm vs.(1.71±0.14)cm, P<0.05)。 结论:GNP-TryRGD-VEGFsiRNA 复合物集靶向浓集与靶向治疗于一体,且可能有助于增强肝癌RFA 的疗效。


General properties and application of VEGF siRNA-loaded RGD-conjugated gold nanoparticles in radiofrequency ablation

Abstract

Objective: To investigate the general properties of the complexes of VEGF siRNA-loaded RGD-conjugated gold nanoparticles (GNPs) (GNPs-TyrRGD-VEGFsiRNA) and their impact on necrotic effect of radiofrequency ablation (RFA) in the liver. Methods: GNPs-TyrRGD-VEGFsiRNA complexes were synthetized by chemical and electrostatic adsorption methods and the discreteness of the complexes was examined by electron microscope. The stability of the VEGF siRNA in the complexes was tested by gel electrophoresis, the cytotoxicity of complexes to normal hepatic cells was determined by CCK-8 assay, the binding capacities of the complexes to normal hepatic cells and liver cancer cells after co-incubation were analyzed by using electron microscopy, and the impact of the complexes on the necrotic effect of RFA were observed in the in-vitro pig liver. Results: The complexes showed a higher discreteness than the naked GNPs and the content of VEGF siRNA in the complexes was approximately equal to the initially loaded content. Both the complexes and naked GNPs exhibited almost no cytotoxicity to the normal hepatic cells at a concentration below 30% and the binding ability of the complexes to the liver cancer cells was significantly greater than that to the normal hepatic cells (P<0.05), but the naked GNPs showed no difference between binding ability to the two types of cells (P>0.05). The lesion diameter induced by RFA with the complexes injected through radiofrequency needle was significantly larger than that in control group with saline injection [(2.19±0.24) cm vs. (1.71±0.14) cm, P<0.05]. Conclusion: GNPs-TryRGD-VEGFsiRNA complexes can integrate targeted concentration and targeted therapy as a whole, and may also be helpful for enhancing the efficacy of liver cancer RFA treatment.


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引用

引用本文: 青 熊, 孟达 邹, 青松 邓, 晓武 李, 宽生 马, 平 别. 载VEGF siRNA 环五肽RGD 偶联纳米金颗粒的基本特性及在射频消融中的应用[J]. 中国普通外科杂志, 2015, 24(1): 45–51.
Cite this article as: XIONG Qing, ZOU Mengda, DENG Qingsong, LI Xiaowu, MA Kuansheng, BIE Ping . General properties and application of VEGF siRNA-loaded RGD-conjugated gold nanoparticles in radiofrequency ablation [J]. Chin J Gen Surg, 2015, 24(1): 45–51.