AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing

作者：Ghatak Subhadip; Li Jilong; Chan Yuk C; Gnyawali Surya C; Steen Erin; Yung Bryant C; Khanna Savita; Roy Sashwati; Lee Robert J; Sen Chandan K^*

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2016, 12(7): 1827-1831.

DOI：10.1016/j.nano.2016.03.004

• Ischemic wounds
• Tissue oxygenation
• miR-210
• Keratinocytes proliferation
• Lipid nanoparticles

Peripheral vasculopathies cause severe wound hypoxia inducing the hypoxamiR miR-210. High level of miR-210, persisting in wound-edge tissue as ischemic memory, suppresses oxidative metabolism and inhibits cell proliferation necessary for healing. In wound-edge tissue of chronic wound patients, elevated miR-210 was tightly associated with inhibition of epidermal cell proliferation as evident by lowered Ki67 immunoreactivity. To inhibit miR-210 in murine ischemic wound-edge tissue, we report the formulation of antihypoxamiR functionalized gramicidin lipid nanoparticles ( AFGLN). A single intradermal delivery of AFGLN encapsulating LNA-conjugated antihypoximiR- 210 ( AFGLN(miR-210)) lowered miR-210 level in the ischemic wound-edge tissue. In repTOP (TM) mitoIRE mice, AFGLN(miR-210) rescued keratinocyte proliferation as visualized by in vivo imaging system ( IVIS). P-31 NMR studies showed elevated ATP content at the ischemic wound-edge tissue following AFGLN(miR-210) treatment indicating recovering bioenergetics necessary for healing. Consistently, AFGLN(miR-210) improved ischemic wound closure. The nanoparticle based approach reported herein is effective for miR-directed wound therapeutics warranting further translational development.

• 出版日期2016-10