Strategy to relieve cellular oxidative stress based on ultra-small nanobubbles without exogenous antioxidants

Reactive oxygen species (ROS) produced in living systems are essential to physiological processes. However, excess ROS in the organism (oxidative stress) damages crucial cell components, leading to many diseases. Although some commercial antioxidants can counteract ROS damage, their inadequate tissue penetration, disruption of normal ROS functions, and possible toxicity have led to disappointing results in clinical trials for ROS-induced chronic diseases. Thus, new antioxidant strategies are warranted. Herein, we report a novel "antioxidant" composed of pure nitrogen gas in an ultra-small nanobubble (UNB) form, which can relieve oxidative stress in cells. Our results indicate that UNBs can reduce cellular ROS levels under oxidative stress and increase survival and proliferation. Besides, UNBs can decrease the oxidative damage to cellular biomacromolecules (lipids, proteins, and nuclear acids). Thus, UNBs are a promising nonchemical antioxidative strategy with potential applications against oxidative stress-related diseases and without the natural defect of chemical antioxidants.