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Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

Gene Therapy volume 12, pages 685–693 (2005)Cite this article

Abstract

Intratracheal injection of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) complexes has been demonstrated to delay the onset and reduce the extent of ionizing irradiation-induced murine pulmonary organizing alveolitis/fibrosis. To facilitate translation of this modality to clinical fractionated radiotherapy, inhalation delivery of MnSOD-PL was developed using an ultrasonic nebulizer. Transgene product was quantitated by immunohistochemical quantitation and pulmonary tissue levels of MnSOD biochemical activity. C57BL/6NHsd female mice demonstrated a plasmid dose-dependent increased expression of MnSOD transgene product over the range of 250 μg–2.5 mg of MnSOD-PL administered over a constant 5 min interval. Delivery of a constant concentration of 500 μg of MnSOD-PL with varying times of administration ranging from 0.5 to 10 min demonstrated optimal MnSOD expression at 5 min. Mice pretreated by inhalation delivery of MnSOD-PL demonstrated significantly improved survival after 20 Gy single fraction irradiation to both lungs compared to LacZ-PL inhalation-treated or irradiated control mice. Mice receiving 10 fractions of 3.5 cGy demonstrated increased pulmonary MnSOD transgene product activity by a protocol of every Monday–Wednesday or daily inhalation of MnSOD-PL. Thus, inhalation radioprotective gene therapy using MnSOD-PL provides a practical and effective method for delivery of lung-specific radioprotection during fractionated radiotherapy protocols in a mouse model.

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Acknowledgements

This research was supported by the NIH Lung Cancer SPORE Grant #P50-CA90440.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    M Carpenter, M W Epperly, A Agarwal, S Nie, L Hricisak, Y Niu & J S Greenberger

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  1. M Carpenter
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Carpenter, M., Epperly, M., Agarwal, A. et al. Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage. Gene Ther 12, 685–693 (2005). https://doi.org/10.1038/sj.gt.3302468

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