Antitumor Effect of TRAIL on Oral Squamous Cell Carcinoma using Magnetic Nanoparticle-Mediated Gene Expression
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.
- 6.Armeanu, S., Lauer, U. M., Smirnow, I., Schenk, M., Weiss, T. S., Gregor, M., et al. (2003). Adenoviral gene transfer of tumor necrosis factor–related apoptosis inducing ligand overcomes an impaired response of hepatoma cells but causes severe apoptosis in primary human hepatocytes. Cancer Research, 63, 2369–2372.PubMedGoogle Scholar
- 7.Jacob, D., Davis, J., Zhu, H., Zhang, L., Teraishi, F., & Wu, S. (2004). Suppressing orthotopic pancreatic tumor growth with a fiber-modified adenovector expressing the TRAIL gene from the human telomerase reverse transcriptase promoter. Clinical Cancer Research, 10, 3535–3541.PubMedCrossRefGoogle Scholar
- 21.Lee, Mei-Hwa, Thomas, James L., Ho, Min-Hsien, Yuan, Ching, & Lin, Hung-Yin. (2010). Synthesis of magnetic molecularly imprinted poly(ethylene-co-vinyl alcohol) nanoparticles and their uses in the extraction and sensing of target molecules in urine. ACS Applied Materials and Interfaces, 2(6), 1729–1736.PubMedCrossRefGoogle Scholar
- 22.Mahmoudi, Morteza, Simchi, Abdolreza, Imani, Mohammad, & Hfeli, Urs O. (2009). Superparamagnetic iron oxide nanoparticles with rigid cross-linked polyethylene glycol fumarate coating for application in imaging and drug delivery. Journal of Physical Chemistry C, 113(19), 8124–8131.CrossRefGoogle Scholar
- 26.Mori, Kohsuke, Kondo, Yuichi, Morimoto, Shotaro, & Yamashita, Hiromi. (2008). Synthesis and multifunctional properties of superparamagnetic iron oxide nanoparticles coated with mesoporous silica involving single-site Ti oxide moiety. Journal of Physical Chemistry C, 112, 397–404.CrossRefGoogle Scholar
- 39.Boussif, O., Lezoualc’h, F., Zanta, M. A., Mergny, M. D., Scherman, D., Demeneix, B., et al. (1995). A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proceedings of the National Academy of Sciences of the United States of America, 92(16), 7297–7301.PubMedCentralPubMedCrossRefGoogle Scholar
- 41.Lee, H., Lee, E., Kim do, K., Jang, N. K., Jeong, Y. Y., & Jon, S. (2006). Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. Journal of the American Chemical Society, 128, 7383–7389.PubMedCrossRefGoogle Scholar