Arginine functionalized peptide dendrimers as potential gene delivery vehicles
Arginine functionalized peptide dendrimers as potential gene delivery vehicles
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精氨酸功能化肽树枝状聚合物作为潜在的基因递送载体
DOI：
10.1016/j.biomaterials.2012.03.030
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发表时间：
2012-06-01
期刊：
影响因子：
14
通讯作者：
Gu, Zhongwei
中科院分区：
文献类型：
--
作者：
Luo, Kui;Li, Caixia;Gu, Zhongwei
寻求高效、安全的基因传递系统已成为基因治疗成功应用的关键因素。多肽树枝状大分子目前被认为是非病毒基因递送载体的优秀候选者。在本研究中，我们报道了基于精氨酸功能化的第5代(G5A)到第6代(G6A)的多肽树枝状大分子载体的合成和表征，以及它们在体外和体内的基因转染中的应用。树枝状大分子可以凝聚pDNA，保护pDNA不被核酸酶消化。原子力显微镜(AFM)和动态光散射(DLS)表明树枝状大分子/DNA粒子的尺寸在180-250 nm范围内。体外研究表明，功能化的多肽树枝状大分子在所有研究细胞上提供了非血清依赖的高转染率，比支化聚醚酰亚胺(PEI)在血清存在下的转染率高2倍以上。分子量为17 kDa的树枝状分子G5A在乳腺肿瘤模型中的转染率是PEI的6倍，体外和体内毒性评价表明，G5A具有良好的生物安全性。而相对分子质量为46 kDa的G6A具有更高的细胞毒性。因此，具有最佳世代的功能化树枝状大分子G5A可能是一种潜在的基因输送载体。(C)2012爱思唯尔有限公司。保留所有权利。
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 vitro and in 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 nm range. In 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 kDa demonstrated 6-fold transfection activity than PEI in breast tumor models, as well as good biosafety proved by in vitro and in vivo toxicity evaluation. However, G6A with molecular weight of 46 kDa showed much higher cytotoxicity. The functionalized dendrimer G5A with optimal generation may be therefore a potential candidate for gene delivery vehicle. (c) 2012 Elsevier Ltd. All rights reserved.