Potential Protective Effect of Nitric Oxide-Releasing Nanofibers in Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury.

Abstract

Nitric oxide (NO) is involved in several physiological processes including vasodilation, angiogenesis, immune response, and wound healing, as well as preventing ischemia/reperfusion injury in many organs such as the heart, liver, lungs, and kidneys. Recently, various NO delivery systems such as nanoparticles, nanorods, and nanofibers have been widely studied as potential therapeutic agents. In particular, NO-releasing nanofibers have been attracting much attention for various medicinal applications including regenerative medicine, wound dressings, and coatings for implantable medical devices, due to their flexible and open architectures. In this study, we prepared biocompatible NO-releasing nanofibers by electrospinning using mixed solutions of polymers and methylaminopropyltrimethoxysilane (MAP3), which was modified with N-diazeniumdiolate as an NO donor. In addition, we evaluated their protective effects on hypoxia/reoxygenation (HR) injury in H9c2 cells. The total NO amount released from the resulting MAP3 nanofibers was 1.26 µmol ·mg-1. From the cytotoxicity evaluation of various weights of NO-releasing nanofibers (0 to 2 mg), we selected 1 mg NO-releasing nanofibers for the subsequent experiments. Pre-treatment with NO-releasing nanofibers before hypoxia induction could provide a cytoprotective effect against HR-induced injury in H9c2 cells. The nanofibers could also effectively inhibit the generation of hydrogen peroxide, which was one major contributor to oxidative damage, as well as 8-hydroxyl-2-deoxyguanosine level as an indicator of oxidative DNA damage. In addition, pre-treatment with NO-releasing nano-fibers in a wound model showed wound healing effects similar to those of normal cells. As a result, N-diazeniumdiolate-modified MAP3 nanofibers might protect H9c2 cells from DNA damage by inhibiting the generation of oxidative stress in HR injury. Therefore, we expect that NO-releasing nanofibers could be utilized as a therapeutic strategy for protecting cardiomyocytes from HR injury.