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

Hyun Ji Park, Joan Lee, Mun Jung Kim, Taek Jin Kang, Yongsu Jeong, Soong Ho Um, Seung-Woo Cho

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9148-9156
Number of pages9
JournalBiomaterials
Volume33
Issue number35
DOIs
Publication statusPublished - 2012 Dec 1

Fingerprint

Gene therapy
Hedgehogs
Genetic Therapy
Wound Healing
Nanoparticles
Esters
Genes
Amines
Skin
Wounds and Injuries
Galactosidases
Tissue
Chemokine CXCL12
Angiogenesis Inducing Agents
Polymerase chain reaction
Blood vessels
Therapeutics
Cytotoxicity
Chemokines
Epidermis

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Park, Hyun Ji ; Lee, Joan ; Kim, Mun Jung ; Kang, Taek Jin ; Jeong, Yongsu ; Um, Soong Ho ; Cho, Seung-Woo. / Sonic hedgehog intradermal gene therapy using a biodegradable poly(β-amino esters) nanoparticle to enhance wound healing. In: Biomaterials. 2012 ; Vol. 33, No. 35. pp. 9148-9156.
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Sonic hedgehog intradermal gene therapy using a biodegradable poly(β-amino esters) nanoparticle to enhance wound healing. / Park, Hyun Ji; Lee, Joan; Kim, Mun Jung; Kang, Taek Jin; Jeong, Yongsu; Um, Soong Ho; Cho, Seung-Woo.

In: Biomaterials, Vol. 33, No. 35, 01.12.2012, p. 9148-9156.

Research output: Contribution to journalArticle

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