H2 O2 -triggered bubble generating antioxidant polymeric nanoparticles as ischemia/reperfusion targeted nanotheranostics

Abstract Overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2 O2 ) leads to oxidative stress, causing inflammation and cellular damages and death. H2 O2 is one of the most stable and abundant ROS and H2 O2 -mediated oxidative stress is considered as a key mediator of cellular and tissue damages during ischemia/reperfusion (I/R) injury. Therefore, H2 O2 could hold tremendous potential as a diagnostic biomarker and therapeutic target for oxidative stress-associated inflammatory conditions such as I/R injury. Here, we report a novel nanotheranostic agent that can express ultrasound imaging and simultaneous therapeutic effects for hepatic I/R treatment, which is based on H2 O2 -triggered CO2 -generating antioxidant poly(vanillin oxalate) (PVO). PVO nanoparticles generate CO2 through H2 O2 -triggered oxidation of peroxalate esters and release vanillin, which exerts antioxidant and anti-inflammatory activities. PVO nanoparticles intravenously administrated remarkably enhanced the ultrasound signal in the site of hepatic I/R injury and also effectively suppressed the liver damages by inhibiting inflammation and apoptosis. To our best understanding, H2 O2 -responsive PVO is the first platform which generates bubbles to serve as ultrasound contrast agents and also exerts therapeutic activities. We therefore anticipate that H2 O2 -triggered bubble-generating antioxidant PVO nanoparticles have great potential for ultrasound imaging and therapy of H2 O2 -associated diseases.