Arginine functionalized peptide dendrimers as potential gene delivery vehicles
- 作者：Kui Luo ; Caixia Li ; Li Li ; Wenchuan She ; Gang Wang ; wgang@scu.edu.cn ; Zhongwei Gu ; zwgu@scu.edu.cn
- 关键词：Dendrimer ; Click chemistry ; Gene delivery ; Transfection efficiency ; Cytotoxicity ; Biocompatibility
- 刊名：Biomaterials
- 出版年：2012
- 期刊代码：7_01429612
- 类别：ms
- 出版时间：June, 2012
- 卷：33
- 期：19
- 页码：4917-4927
- 文件大小：2020 K
摘要
The quest for highly efficient and safe gene delivery systems has become the key factor for successful application of gene therapy. Peptide dendrimers are currently investigated as excellent candidates for non-viral gene delivery vectors. In this study, we report the synthesis and characterization of arginine functionalized peptide dendrimer-based vectors ranging from 5th generation (G5A) to 6th generation (G6A) via click chemistry, and their use for gene transfection in聽vitro and in聽vivo. The dendrimers can condense plasmid DNA (pDNA) and protect pDNAs from nuclease digestion. Both atomic force microscopy (AFM) and dynamic light scattering (DLS) revealed that the sizes of dendrimer/DNA particles were within 180-250聽nm range. In聽vitro studies showed that the functionalized peptide dendrimers provided serum independent and high transfection efficiency on all studied cells, as over 2 fold higher than that of branched polyetherimide (PEI) in the presence of serum. Dendrimer G5A with molecular weight of 17聽kDa demonstrated 6-fold transfection activity than PEI in breast tumor models, as well as good biosafety proved by in聽vitro and in聽vivo toxicity evaluation. However, G6A with molecular weight of 46聽kDa showed much higher cytotoxicity. The functionalized dendrimer G5A with optimal generation may be therefore a potential candidate for gene delivery vehicle.