Mol Pharm. 2012 Aug 3. [Epub ahead of print]
Mesenchymal stem cells as a novel carrier for targeted-delivery of gene in cancer therapy based on non-viral transfection.
Abstract
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-base 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 non-viral vector, PEI600-Cyd, prepared by linking low molecular weight polyethylenimine (PEI) and β-cyclodextrin (β-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 non-viral vector was evaluated. The in vitro expression of TRAIL from MSCs-TRAIL was demonstrated by both ELISA and western blot analysis. Furthermore, lung tumor homing ability of MSCs was confirmed by the in vitro and in vivo model. Moreover, the therapeutic effects as well as the safety of MSCs-TRAIL on lung metastases of C57BL/6 mice were also demonstrated. Our results supported both the effectiveness of non-viral vectors in transferring the therapeutic gene to MSCs and the feasible 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 non-viral gene recombination.
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