title: AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing.
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-210rescued 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-210treatment indicating recovering bioenergetics necessary for healing. Consistently, AFGLNmiR-210improved ischemic wound closure. The nanoparticle based approach reported herein is effective for miR-directed wound therapeutics warranting further translational development.
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Subhadip
authors.initials: S
authors.lastname: Ghatak
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Jilong
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Yuk C
authors.initials: YC
authors.lastname: Chan
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Surya C
authors.initials: SC
authors.lastname: Gnyawali
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Steen
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Bryant C
authors.initials: BC
authors.lastname: Yung
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Khanna
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Center for Regenerative Medicine & Cell-Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: chandan.sen@osumc.edu.
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D006096:Gramicidin / Q000008:administration & dosage*; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D015603:Keratinocytes; D008055:Lipids; D051379:Mice; D035683:MicroRNAs; D053758:Nanoparticles; D014945:Wound Healing
chemical_list: D000900:Anti-Bacterial Agents; D008055:Lipids; D035683:MicroRNAs; D006096:Gramicidin
keywords: Ischemic wounds; Keratinocytes proliferation; Lipid nanoparticles; Tissue oxygenation; miR-210