Open AccessLipid nanoparticles silence tumor necrosis factor α to improve wound healing in diabetic mice
Author(s) -
Kasiewicz Lisa N.,
Whitehead Kathryn A.
Publication year - 2019
Publication title -
bioengineering and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2380-6761
DOI - 10.1002/btm2.10123
Subject(s) - tumor necrosis factor alpha , wound healing , medicine , gene knockdown , diabetes mellitus , apoptosis , small interfering rna , necrosis , diabetic foot ulcer , cancer research , immune system , diabetic foot , surgery , immunology , rna , endocrinology , chemistry , gene , biochemistry
Diabetes mellitus is a mounting concern in the United States, as are the mortality and morbidity that result from its complications. Of particular concern, diabetes patients frequently suffer from impaired wound healing and resultant nonhealing diabetic foot ulcers. These ulcers overproduce tumor necrosis factor α (TNFα), which reduces wound bed cell migration and proliferation while encouraging apoptosis. Herein, we describe the use of siRNA‐loaded lipid nanoparticles (LNPs) as a potential wound treatment to combat an overzealous immune response and facilitate wound closure. LNPs were formulated with an ionizable, degradable lipidoid and siRNA specific for TNFα. Topical application of nanoparticles reduced TNFα mRNA expression in the wound by 40–55% in diabetic and nondiabetic mice. In diabetic mice, this TNFα knockdown accelerated wound healing compared to untreated controls. Together, these results serve as proof‐of‐concept that RNA interference therapy using LNPs can reduce the severity and duration of chronic diabetic wounds.