Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display
Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display
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使用噬菌体展示鉴定的软骨细胞归巢肽将非病毒载体靶向递送至体内软骨
DOI：
10.1016/j.biomaterials.2011.05.017
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发表时间：
2011-09-01
期刊：
影响因子：
14
通讯作者：
Ao, Yingfang
中科院分区：
文献类型：
--
作者：
Pi, Yanbin;Zhang, Xin;Ao, Yingfang
基因治疗是治疗骨关节炎和软骨损伤的一种很有前途的方法。然而，将靶基因特异性地递送到软骨细胞中是一个巨大的挑战，因为它们的非血管分布和软骨的致密细胞外基质。在我们的研究中，我们确定了一个软骨细胞亲和肽（CAP，DWRVIIPPRPSA）的噬菌体展示技术。随后的分析表明，该肽可以有效地与软骨细胞特异性相互作用，而没有任何种属特异性。将CAP共价修饰聚乙烯亚胺（PEI），构建软骨靶向治疗的非病毒载体。为了研究CAP修饰载体的软骨靶向特性，将FITC标记的CAP缀合的PEI/DNA颗粒注射到兔膝关节中，并在共聚焦显微镜下观察。与随机乱序肽（SP）修饰的载体相比，在软骨中检测到更高浓度的CAP修饰的载体，并且特异性地被软骨细胞吸收。为了评估软骨靶向转染效率，使用CAP和SP修饰的PEI将GFP和荧光素酶基因递送到膝关节中。CAP修饰的PEI介导的Carcinoma转染比SP修饰的PEI更有效和特异。这一结果表明，CAP修饰的PEI可用作软骨疾病的特异性软骨靶向载体。(C)2011爱思唯尔有限公司版权所有。
Gene therapy is a promising method for osteoarthritis and cartilage injury. However, specifically delivering target genes into chondrocytes is a great challenge because of their non-vascularity and the dense extracellular matrix of cartilage. In our study, we identified a chondrocyte-affinity peptide (CAP, DWRVIIPPRPSA) by phage display technology. Subsequent analysis suggests that the peptide can efficiently interact specifically with chondrocytes without any species specificity. Polyethylenimine (PEI) was covalently modified with CAP to construct a non-viral vector for cartilage-targeted therapy. To investigate the cartilage-targeting property of the CAP-modified vector, FITC-labeled CAP conjugated PEI/DNA particles were injected into rabbit knee joints, and visualized under confocal microscope. Higher concentrations of CAP-modified vector were detected in the cartilage and specifically taken up by chondrocytes compared with a randomly scrambled peptide (SP)-modified vector. To evaluate cartilage-targeting transfection efficiency, the GFP and luciferase genes were delivered into knee joints using CAP- and SP-modified PEI. Cartilage transfections mediated by CAP-modified PEI were much more efficient and specific than those by SP-modified PEI. This result suggests that CAP-modified PEI could be used as a specific cartilage-targeting vector for cartilage disorders. (C) 2011 Elsevier Ltd. All rights reserved.