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整合素配体RGD修饰的阳离子脂质体作为siRNA输送载体的体外研究
引用本文:杨世进,杨丽娟,姜娟,王坚成,张强.整合素配体RGD修饰的阳离子脂质体作为siRNA输送载体的体外研究[J].中国药学,2008,17(2):97-105.
作者姓名:杨世进  杨丽娟  姜娟  王坚成  张强
作者单位:北京大学药学院药剂学系,北京100083
基金项目:国家自然科学基金 , 国家重点基础研究发展计划(973计划) , 北京市自然科学基金 , 高等学校博士学科点专项科研项目
摘    要:本研究构建了能够靶向肿瘤新生血管的RGD修饰阳离子脂质体(RGD-Lipo),作为靶向耐药相关基因MDR1的siRNA输送载体并评价其相关的药剂学性质。该脂质体与siRNA形成的复合物粒径控制在200nm以内,并且对其中所包载的siRNA具有一定的保护作用。体外实验结果表明,经RGD修饰的脂质体(RGD-Lipo)细胞粘附能力显著增强,并可增加细胞内siRNA的转染效果。与利用前插法进行靶向修饰相比,利用后插法进行RGD修饰可有效地改善siRNA的溶酶体释放效率。细胞毒试验结果表明,后插法制备的pRGD-Lipo-siRNA能够有效逆转人卵巢癌SKV03/A细胞的耐药性,并增加阿霉素药物在细胞内的蓄积。体外研究结果证实,使用pRGD-Lipo-siRNA有利于提高耐药细胞对化疗药阿霉素的敏感度,并将有可能应用于临床耐药肿瘤的治疗。

关 键 词:siRNA  阳离子脂质体  DC-Chol  整合素RGD

In vitro investigation of RGD-modified stabilized cationic liposomes as non-viral vehicle for siRNA delivery
Shi-Jin Yang,Li-Juan Yang,Juan Jiang,Jian-Cheng Wang,Qiang Zhang.In vitro investigation of RGD-modified stabilized cationic liposomes as non-viral vehicle for siRNA delivery[J].Journal of Chinese Pharmaceutical Sciences,2008,17(2):97-105.
Authors:Shi-Jin Yang  Li-Juan Yang  Juan Jiang  Jian-Cheng Wang  Qiang Zhang
Institution:(Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China)
Abstract:In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared with a narrow size distribution below 200 nm. It was shown that the encapsulated siRNA in the liposomes could be effectively protected from serum degradation. Also, enhanced cell binding and intracellular uptake of siRNA in the doxorubicin-resistant human ova- rian cancer cell lines SKOV3/A were found in RGD-Lipo-siRNA preparation as compared to that of unmodified cationic lipsomes (Lipo-siRNA). Using the post-insertion method for RGD modification, lysosome release of siRNA in pRGD-Lipo-siRNA was improved. From flow cytometry, significant increase of doxorubicin accumulation was observed in the SKOV3/A cells treated with pRGD-Lipo-siRNA targeting human MDR1 gene. In vitro cytotoxicity assay showed that the significant cell growth inhibition was achieved in the SKOV3/A cells after treating with the combined use of siRNA and doxorubicin. In conclusions, postinserted RGD modified lipoplex, pRGD-Lipo-siRNA, was successfully used for siRNA transfection and achieved drug resistance reversal in human ovarian cancer SKOV3/A (doxorubicin-resistant) cells. It suggested that this liposomes might be a potential vehicle for siRNA delivery in vivo.
Keywords:siRNA  Cationic liposomes  DC-Chol  RGD modification
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