An MRI-visible non-viral vector bearing GD2 single chain antibody for targeted gene delivery to human bone marrow mesenchymal stem cells.
An MRI-visible non-viral vector bearing GD2 single chain antibody for targeted gene delivery to human bone marrow mesenchymal stem cells.
复制标题
一种 MRI 可见的非病毒载体，带有 GD2 单链抗体，用于将靶向基因递送至人骨髓间充质干细胞。
DOI：
10.1371/journal.pone.0076612
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shuai X
中科院分区：
文献类型：
--
作者：
Pang P;Wu C;Shen M;Gong F;Zhu K;Jiang Z;Guan S;Shan H;Shuai X
神经节苷脂GD 2是一种新的表面标记物，仅在正常骨髓中的人骨髓间充质干细胞上表达。在这项研究中，MRI可见的，有针对性的，非病毒载体的有效基因传递到人骨髓间充质干细胞，首先合成的靶向配体，GD 2单链抗体（scAbGD 2），PEG-g-PEI-SPION的远端。然后将靶向载体用于浓缩质粒DNA以形成显示稳定的小尺寸、低细胞毒性和良好生物相容性的纳米颗粒。报告基因检测结果显示，靶向复合物对人骨髓间充质干细胞的转染效率最高，为59.6% ± 4.5%，高于非靶向复合物和脂质体/pDNA的转染效率（分别为17.7% ± 2.9%和34.9% ± 3.6%）（P<0.01）。因此，与非靶向组相比，在靶向组的纤维化大鼠肝脏中观察到更多的体内基因表达。此外，scAbGD 2-PEG-g-PEI-SPION的靶向能力通过共聚焦激光扫描显微镜、普鲁士蓝染色和磁共振成像成功地在体外验证。我们的研究结果表明，scAbGD 2-PEG-g-PEI-SPION是一个有前途的MRI可见的非病毒载体的靶向基因传递到人骨髓间充质干细胞。
The neural ganglioside GD2 has recently been reported to be a novel surface marker that is only expressed on human bone marrow mesenchymal stem cells within normal marrow. In this study, an MRI-visible, targeted, non-viral vector for effective gene delivery to human bone marrow mesenchymal stem cells was first synthesized by attaching a targeting ligand, the GD2 single chain antibody (scAbGD2), to the distal ends of PEG-g-PEI-SPION. The targeted vector was then used to condense plasmid DNA to form nanoparticles showing stable small size, low cytotoxicity, and good biocompatibility. Based on a reporter gene assay, the transfection efficiency of targeting complex reached the highest value at 59.6% ± 4.5% in human bone marrow mesenchymal stem cells, which was higher than those obtained using nontargeting complex and lipofectamine/pDNA (17.7% ± 2.9% and 34.9% ± 3.6%, respectively) (P<0.01). Consequently, compared with the nontargeting group, more in vivo gene expression was observed in the fibrotic rat livers of the targeting group. Furthermore, the targeting capacity of scAbGD2-PEG-g-PEI-SPION was successfully verified in vitro by confocal laser scanning microscopy, Prussian blue staining, and magnetic resonance imaging. Our results indicate that scAbGD2-PEG-g-PEI-SPION is a promising MRI-visible non-viral vector for targeted gene delivery to human bone marrow mesenchymal stem cells.
登录
查看更多内容
影响因子：
14
作者：
Ahn, Hyun Hee;Lee, Jung Hwa;Lee, Hai Bang
通讯作者：
Lee, Hai Bang
影响因子：
20.3
作者：
Martinez, Caridad;Hofmann, Ted J.;Horwitz, Edwin M.
通讯作者：
Horwitz, Edwin M.
影响因子：
4.1
作者：
Thibault, Richard A.;Baggett, L. Scott;Kasper, F. Kurtis
通讯作者：
Kasper, F. Kurtis
影响因子：
4
作者：
Barzilay, Ran;Ben-Zur, Tali;Offen, Daniel
通讯作者：
Offen, Daniel
影响因子：
11.2
作者：
Loebinger MR;Eddaoudi A;Davies D;Janes SM
通讯作者：
Janes SM