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  • sonic hedgehog intradermal gene therapy using a biodegradable poly(β-amino esters) nanoparticle to enhance wound healing

    جزئیات بیشتر مقاله
    • تاریخ ارائه: 1391/01/01
    • تاریخ انتشار در تی پی بین: 1391/01/01
    • تعداد بازدید: 589
    • تعداد پرسش و پاسخ ها: 0
    • شماره تماس دبیرخانه رویداد: -
     biodegradable cationic poly(β-amino esters) (pbae) nanoparticles are promising tools for delivering genes into various types of cells and tissues. specific end-modification of the pbae terminal parts significantly improves the efficiency of gene delivery in vitro and in vivo, and reduces cytotoxicity. here, we demonstrated that amine end-modified pbae nanoparticles can be used for intradermal delivery of therapeutic genes for wound healing in an animal skin wound model. sonic hedgehog (shh), a prototypical morphogen with angiogenic potential, was applied as a therapeutic gene to regenerate skin tissue. amine end-modified pbaes showed higher gene transfection efficiency in vitro than the commercial reagent, lipofectamine 2000. intradermal delivery of the shh gene using amine end-modified pbaes was tested in a readout mouse model of shh signaling. we evaluated its therapeutic efficacy in mice with full-thickness skin wounds. shh gene therapy significantly increased the expression of the angiogenic growth factor, vascular endothelial growth factor, and the stromal cell-derived factor-1α chemokine within the wounded regions early after injection. ultimately, wound closure was accelerated in mice receiving the pbae/shh gene therapy compared to mice receiving intradermal delivery of a control gene (β-galactosidase plasmid) by pbae nanoparticles. quantitative real-time polymerase chain reaction and histological analysis revealed that there were significant improvements in epidermis regeneration and blood vessel formation in the mice treated with pbae/shh nanoparticles. in conclusion, shh intradermal gene therapy using biodegradable pbae nanoparticles is a potential treatment to promote wound healing.

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