Nanocrystals continuously releasing nitric oxide: Promoting cell migration and increasing cell survival against oxidative stress

Antioxidants offer a potential cure for certain diseases caused by reactive oxygen species (ROS); unfortunately, conventional antioxidants have poor long-term targeting and bioavailability. Here, we report NO-releasing crystals (NOCs) to achieve direct ROS scavenging as well as enhance cell survival, based on their long-term NO supply. Despite the controversial functions of NO, in order to achieve the goal, NOCs can supply a constant level of NO over 4 days, owing to the thermally stable form of C-diazeniumdiolate-based NO donor. NOCs are controllable for their size, aspect ratio, and NO loading by the crystallization temperature; the nanosized NOCs enhanced cytocompatibility and cell migration owing to their excellent distribution and supply of NO at physiological levels. In addition, NOCs exhibited efficient and continuous radical scavenging compared to ascorbic acid (AA) as a function of the NO release amount. An in vitro test on the antioxidative activity of NO was investigated via two methods: pretreatment of antioxidants prior to oxidative stress and antioxidant treatment in the presence of the oxidants. It was found that 10−20 μM of NO from NOC was optimal for cell protection under oxidative stress. These findings demonstrate the controlled NO system and potential utility of NO as an effective antioxidation tool for treating diseases induced by ROS overproduction.