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Antitumor Effect of TRAIL on Oral Squamous Cell Carcinoma using Magnetic Nanoparticle-Mediated Gene Expression

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Abstract

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.

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Acknowledgments

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 Nan**g City (No. 2011-19-198*), the Third Level Fund for the Young Talents in the Health Field of Nan**g City. We thank Dr. Shenglin Li at Peking University, China for a gift of the Tca83 cell line.

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Authors and Affiliations

  1. Institute and Hospital of Stomatology, Nan**g University Medical School, Nan**g, 210008, China

    Leiying Miao, Chao Liu, Jiuyu Ge, Weidong Yang, Weibin Sun & Qingang Hu

  2. School of Stomatology, Jilin University, Changchun, 130041, China

    **zhong Liu & Hongchen Sun

  3. State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130041, China

    Bai Yang

  4. Molecular Physiology and Therapeutics Branch, DHHS, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA

    Changyu Zheng

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  1. Leiying Miao
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Correspondence to Hongchen Sun or Qingang Hu.

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Leiying Miao and Chao Liu have contributed to this work equally.

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Miao, L., Liu, C., Ge, J. et al. Antitumor Effect of TRAIL on Oral Squamous Cell Carcinoma using Magnetic Nanoparticle-Mediated Gene Expression. Cell Biochem Biophys 69, 663–672 (2014). https://doi.org/10.1007/s12013-014-9849-z

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