AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing.
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| Abstract |
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 anti-hypoximiR-210 (AFGLNmiR-210) lowered miR-210 level in the ischemic wound-edge tissue. In repTOP™mitoIRE mice, AFGLNmiR-210 rescued keratinocyte proliferation as visualized by in vivo imaging system (IVIS). 31P NMR studies showed elevated ATP content at the ischemic wound-edge tissue following AFGLNmiR-210 treatment indicating recovering bioenergetics necessary for healing. Consistently, AFGLNmiR-210 improved ischemic wound closure. The nanoparticle based approach reported herein is effective for miR-directed wound therapeutics warranting further translational development.
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| Authors | Subhadip Ghatak, Jilong Li, Yuk C Chan, Surya C Gnyawali, Erin Steen, Bryant C Yung, Savita Khanna, Sashwati Roy, Robert J Lee, Chandan K Sen |
| Journal | Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 12 Issue 7 Pg. 1827-1831 (10 2016) ISSN: 1549-9642 [Electronic] United States |
| PMID | 27033464 (Publication Type: Journal Article) |
| Copyright | Copyright © 2016 Elsevier Inc. All rights reserved. |
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