Use of Cerium Oxide Nanoparticles Conjugated with MicroRNA-146a to Correct the Diabetic Wound Healing Impairment

Abstract

BACKGROUND: Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds. STUDY DESIGN: Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus. RESULTS: Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance. CONCLUSIONS: We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application.