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Study on the Multidrug Resistance 1 Gene Transfection Efficiency Using Adenovirus Vector Enhanced by Ultrasonic Microbubbles In Vitro

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Abstract

As gene delivery reagents, microbubbles have been successfully used in combination with ultrasound. Shock wave exposure has been shown to transfect cells with naked DNA in vitro, but it has not been tested whether the addition of microbubbles would enhance DNA uptake with adenovirus vector. Therefore, the aim of this study was to study the efficacy and safety of multidrug resistance 1 (MDR1) gene transfer into the bone marrow mononuclear cells of rabbits using adenovirus vector enhanced by ultrasound with microbubbles in vitro. The transfection rate of the MDR1 gene was significantly increased by ultrasound microbubbles with adenovirus. After ultrasonic irradiation, there were transient holes in the cell membrane, which disappeared after irradiation by ultrasound for 24 h. The temporary swelling of the organelles was reversible. Our in vitro findings conclusively demonstrate that the exogenous MDR1 gene transfer into the mononuclear cells of rabbits with adenovirus vector was enhanced by the ultrasonic microbubbles and this transfection technique is safe.

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References

  1. Guo, C., & Jin, X. (2006). Chemoprotection effect of multidrug resistance 1 (MDR1) gene transfer to hematopoietic progenitor cells and engrafted in mice with cancer allows intensified chemotherapy. Cancer Investigation, 24(7), 659–668.

    Article  CAS  Google Scholar 

  2. Kang, Q., Jin, X., Li, Y., An, S., Wang, S., & Xu, J. (2002). Expression of Mdr1 gene in a murine bone marrow transplantation model. Zhonghua Xue Ye Xue Za Zhi, 23(8), 400–402.

    CAS  Google Scholar 

  3. Wang, Y., Jin, X. Q., Wang, S., Wang, Q., Luo, Q., & Luo, X. J. (2006). Therapeutic efficacy and bone marrow protection of the mdr1 gene and over-dose chemotherapy with doxorubicin for rabbits with VX2 hepatocarcinoma. Hepatobiliary & Pancreatic Diseases International, 5(4), 545–551.

    CAS  Google Scholar 

  4. Bekeredjian, R., Katus, H. A., & Kuecherer, H. F. (2006). Therapeutic use of ultrasound targeted microbubble destruction: A review of non-cardiac applications. Ultraschall in der Medizin, 27, 134–140.

    Article  CAS  Google Scholar 

  5. Ayme-Bellegarda, E. J. (1990). Collapse and rebound of a gas-filled spherical bubble immersed in a diagnostic ultrasonic field. Journal of the Acoustical Society of America, 88, 1054–1060.

    Article  CAS  Google Scholar 

  6. van Wamel, A., Bouakaz, A., Versluis, M., & de Jong, N. (2004). Micromanipulation of endothelial cells: Ultrasound-microbubble-cell interaction. Ultrasound in Medicine and Biology, 30, 1255–1258.

    Article  Google Scholar 

  7. Marmottant, P., & Hilgenfeldt, S. (2003). Controlled vesicle deformation and lysis by single oscillating bubbles. Nature, 423, 153–156.

    Article  CAS  Google Scholar 

  8. Wu, J. (2002). Theoretical study on shear stress generated by microstreaming surrounding contrast agents attached to living cells. Ultrasound in Medicine and Biology, 28, 125–129.

    Article  Google Scholar 

  9. Postema, M., van Wamel, A., Lancée, C. T., & de Jong, N. (2004). Ultrasound-induced encapsulated microbubble phenomena. Ultrasound in Medicine and Biology, 30, 827–840.

    Article  Google Scholar 

  10. Miller, D. L., & Quddus, J. (2001). Lysis and sonoporation of epidermoid and phagocytic monolayer cells by diagnostic ultrasound activation of contrast agent gas bodies. Ultrasound in Medicine and Biology, 27, 1107–1113.

    Article  CAS  Google Scholar 

  11. Deng, C. X., Sieling, F., Pan, H., & Cui, J. (2004). Ultrasound-induced cell membrane porosity. Ultrasound in Medicine and Biology, 30, 519–526.

    Article  Google Scholar 

  12. Miller, D. L., Dou, C., & Song, J. (2003). DNA transfer and cell killing in epidermoid cells by diagnostic ultrasound activation of contrast agent gas bodies in vitro. Ultrasound in Medicine and Biology, 29, 601–607.

    Article  Google Scholar 

  13. Lawrie, A., Brisken, A. F., Francis, S. E., Cumberland, D. C., Crossman, D. C., & Newman, C. M. (2000). Microbubble-enhanced ultrasound for vascular gene delivery. Gene Therapy, 7, 2023–2027.

    Article  CAS  Google Scholar 

  14. Frenkel, P. A., Chen, S., Thai, T., Shohet, R. V., & Grayburn, P. A. (2002). DNA-loaded albumin microbubbles enhance ultrasound-mediated transfection in vitro. Ultrasound in Medicine and Biology, 28, 817–822.

    Article  Google Scholar 

  15. Christiansen, J. P., French, B. A., Klibanov, A. L., Kaul, S., & Lindner, J. R. (2003). Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles. Ultrasound in Medicine and Biology, 29, 1759–1767.

    Article  Google Scholar 

  16. Lu, Q. L., Liang, H. D., Partridge, T., & Blomley, M. J. (2003). Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage. Gene Therapy, 10, 396–405.

    Article  CAS  Google Scholar 

  17. Miller, D. L., & Song, J. (2003). Tumor growth reduction and DNA transfer by cavitation-enhanced high-intensity focused ultrasound in vivo. Ultrasound in Medicine and Biology, 29, 887–893.

    Article  Google Scholar 

  18. Bekeredjian, R., Chen, S., Frenkel, P. A., Grayburn, P. A., & Shohet, R. V. (2003). Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation, 108, 1022–1026.

    Article  Google Scholar 

  19. Korpanty, G., Chen, S., Shohet, R. V., Ding, J., Yang, B., Frenkel, P. A., et al. (2005). Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles. Gene Therapy, 12, 1305–1312.

    Article  CAS  Google Scholar 

  20. Klibanov, A. L. (2005). Ligand-carrying gas-filled microbubbles: Ultrasound contrast agents for targeted molecular imaging. Bioconjugate Chemistry, 16, 9–17.

    Article  CAS  Google Scholar 

  21. Lindner, J. R. (2004). Molecular imaging with contrast ultrasound and targeted microbubbles. Journal of Nuclear Cardiology, 11, 215–221.

    Article  Google Scholar 

  22. He, T. C., Zhou, S., da Costa, L. T., Yu, J., Kinzler, K. W., & Vogelstein, B. (1998). A simplified system for generating recombinant adenoviruses. Proceedings of the National Academy of Sciences of the United States of America, 95(5), 2509–2514.

    Article  CAS  Google Scholar 

  23. Luo, J., Deng, Z. L., Luo, X., Tang, N., Song, W. X., Chen, J., et al. (2007). A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nature Protocols, 2(5), 1236–1247.

    Article  CAS  Google Scholar 

  24. Siddiqui, A., Kerb, R., Weale, M. E., Brinkmann, U., Smith, A., Goldstein, D. B., et al. (2003). Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. New England Journal of Medicine, 348, 1442–1448.

    Article  CAS  Google Scholar 

  25. Donnelly, J., Berry, K., & Ulmer, J. B. (2003). Technical and regulatory hurdles for DNA vaccines. International Journal for Parasitology, 33, 457–467.

    Article  CAS  Google Scholar 

  26. Brown, M. D., Scha¨tzlein, A. G., & Uchegbu, I. F. (2001). Gene delivery with synthetic (non viral) carriers. International Journal of Pharmaceutics, 229, 1–21.

    Article  CAS  Google Scholar 

  27. Michel, M. S., Erben, P., Trojan, L., Schaaf, A., Kiknavelidze, K., Knoll, T., et al. (2004). Acoustic energy: A new transfection method for cancer of the prostate, cancer of the bladder and benign kidney cells. Anticancer Research, 24, 2303–2308.

    CAS  Google Scholar 

  28. Fischer, A. J., Stanke, J. J., Omar, G., Askwith, C. C., & Burry, R. W. (2006). Ultrasound-mediated gene transfer into neuronal cells. Journal of Biotechnology, 122, 393–411.

    Article  CAS  Google Scholar 

  29. Yamamoto, N., Hayashi, Y., Kagami, H., Fukui, T., Fukuhara, H., Tohnai, I., et al. (2005). Suicide gene therapy using adenovirus vector for human oral squamous carcinoma cell line in vitro. Nagoya Journal of Medical Science, 67(3–4), 83–91.

    CAS  Google Scholar 

  30. Wang, J. F., Wang, J. B., Chen, H., Zhang, C. M., Liu, L., Pan, S. H., et al. (2008). Ultrasound-mediated microbubble destruction enhance gene transfection in pancreatic cancer cells. Advances in Therapy, 25(5), 412–421.

    Article  CAS  Google Scholar 

  31. Guzmán, H. R., Nguyen, D. X., Khan, S., & Prausnitz, M. R. (2001). Ultrasound-mediated disruption of cell membranes. I. Quantification of molecular uptake and cell viability. Journal of the Acoustical Society of America, 110, 588–596.

    Article  Google Scholar 

  32. Mayer, C. R., Geis, N. A., Katus, H. A., & Bekeredjian, R. (2008). Ultrasound targeted microbubble destruction for drug and gene delivery. Expert Opinion on Drug Delivery, 5(10), 1121–1138.

    Article  CAS  Google Scholar 

  33. Tinkov, S., Bekeredjian, R., Winter, G., & Coester, C. (2009). Microbubbles as ultrasound triggered drug carriers. Journal of Pharmaceutical Sciences, 98(6), 1935–1961.

    Article  CAS  Google Scholar 

  34. Dalecki, D. (2007). WFUMB safety symposium on echo-contrast agents: Bioeffects of ultrasound contrast agents in vivo. Ultrasound in Medicine and Biology, 33(2), 205–213.

    Article  Google Scholar 

  35. ter Haar, G. (2009). Safety and bio-effects of ultrasound contrast agents. Medical and Biological Engineering and Computing, 47(8), 893–900.

    Article  Google Scholar 

  36. Lai, C. Y., Wu, C. H., Chen, C. C., & Li, P. C. (2006). Quantitative relations of acoustic inertial cavitation with sonoporation and cell viability. Ultrasound in Medicine and Biology, 32(12), 1931–1941.

    Article  Google Scholar 

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Correspondence to Yi Wang.

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Guo, Z., Hong, S., Jin, X. et al. Study on the Multidrug Resistance 1 Gene Transfection Efficiency Using Adenovirus Vector Enhanced by Ultrasonic Microbubbles In Vitro. Mol Biotechnol 48, 138–146 (2011). https://doi.org/10.1007/s12033-010-9354-6

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