Mesenchymal Stem Cells as a Novel Carrier for Targeted Delivery of Gene in Cancer Therapy Based on Nonviral Transfection

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• 作者：Yu-Lan Hu ; Bin Huang ; Tian-Yuan Zhang ; Pei-Hong Miao ; Gu-Ping Tang ; Yasuhiko Tabata ; Jian-Qing Gao
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：September 4, 2012
• 年：2012
• 卷：9
• 期：9
• 页码：2698-2709
• 全文大小：528K
• 年卷期：v.9,no.9(September 4, 2012)
• ISSN：1543-8392

文摘

The success of gene therapy relies largely on an effective targeted gene delivery system. Till recently, more and more targeted delivery carriers, such as liposome, nanoparticles, microbubbles, etc., have been developed. However, the clinical applications of these systems were limited for their several disadvantages. Therefore, design and development of novel drug/gene delivery vehicles became a hot topic. Cell-based delivery systems are emerging as an alternative for the targeted delivery system as we described previously. Mesenchymal stem cells (MSCs) are an attractive cell therapy carrier for the delivery of therapeutic agents into tumor sites mainly for their tumor-targeting capacities. In the present study, a nonviral vector, PEI₆₀₀-Cyd, prepared by linking low molecular weight polyethylenimine (PEI) and 尾-cyclodextrin (尾-CD), was used to introduce the therapeutical gene, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), to MSCs. Meanwhile, the characterization, transfection efficiency, cytotoxicity, cellular internalization, and its mechanism of this nonviral vector were evaluated. The in vitro expression of TRAIL from MSCs-TRAIL was demonstrated by both enzyme-linked immunosorbent assay and Western blot analysis. The lung tumor homing ability of MSCs was further confirmed by the in vitro and in vivo model. Moreover, the therapeutic effects as well as the safety of MSCs-TRAIL on lung metastases bearing C57BL/6 mice and normal C57BL/6 mice were also demonstrated. Our results supported both the effectiveness of nonviral vectors in transferring the therapeutic gene to MSCs and the feasibility of using MSCs as a targeted gene delivery carrier, indicating that MSCs could be a promising tumor target delivery vehicle in cancer gene therapy based on nonviral gene recombination.

Keywords:

MSCs; tumor targeting; TRAIL; PEI₆₀₀-Cyd; gene recombination