Antitumor Effect of TRAIL on Oral Squamous Cell Carcinoma using Magnetic Nanoparticle-Mediated Gene Expression
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We developed a new magnetic nanovector to improve the efficiency and targeting of transgene therapy for oral squamous cell carcinoma (OSCC). Positively charged polymer PEI-modified Fe3O4 magnetic nanoparticles were tested as gene transfer vectors in the presence of a magnetic field. The Fe3O4 nanoparticles were prepared by a co-precipitation method and had good dispersibility in water. These nanoparticles modified by PEI were combined with negatively charged pACTERT-EGFP via electrostatic interaction. The transfection efficiency of the magnetic nano-gene vector with the magnetic field was determined by a fluorescence-inverted microscope and flow cytometry. The results showed significant improvement compared with the control group (p < 0.05). The magnetic complexes also exhibited up to 6-times higher transfection efficiency compared with commonly used PEI or lipofectin. On the basis of these results, the antitumor effect with suicide gene therapy using pACTERT-TRAIL in vitro and vivo was evaluated. In vitro apoptosis was determined with the Annexin V-FITC Apoptosis Detection Kit. The results suggested that PEI-modified Fe3O4 nanoparticles could mediate the killing of Tca83 cells. Furthermore, treatment with pACTERT-TRAIL delivered by magnetic nanoparticles showed a significant cytostatic effect through the induction of apoptosis in a xenograft model. This indicates that magnetic nano-gene vectors could improve the transgene efficiency for Tca83 cells and could exhibit antitumor functions with the plasmid pACTERT-TRAIL. This may be a new way to treat OSCC.
KeywordsOral squamous cell carcinoma Nanoparticles Polyethylenimine Apoptosis
This work was supported by grants from the National Natural Science Foundation of China (No: 81300852, 30672338, 30740420551 and 30830108), Jiangsu Province Natural Science Foundation of China (BK20130079), the Youth Start Fund of Nanjing City (No. 2011-19-198*), the Third Level Fund for the Young Talents in the Health Field of Nanjing City. We thank Dr. Shenglin Li at Peking University, China for a gift of the Tca83 cell line.
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