Lee, DongwonBae, SoochanHong, DonghyunLim, HyungsukYoon, Joo HeungHwang, OnPark, SeunggyuKe, QingenKhang, GilsonKang, Peter2014-02-182013Lee, Dongwon, Soochan Bae, Donghyun Hong, Hyungsuk Lim, Joo Heung Yoon, On Hwang, Seunggyu Park, Qingen Ke, Gilson Khang, and Peter M. Kang. 2013. “H2O2-responsive molecularly engineered polymer nanoparticles as ischemia/reperfusion-targeted nanotherapeutic agents.” Scientific Reports 3 (1): 2233. doi:10.1038/srep02233. http://dx.doi.org/10.1038/srep02233.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717603The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the most abundant form of ROS produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. Here, we report H2O2-responsive antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA) (PVAX) as a novel I/R-targeted nanotherapeutic agent. PVAX was designed to incorporate VA and H2O2-responsive peroxalate ester linkages covalently in its backbone. PVAX nanoparticles therefore degrade and release VA, which is able to reduce the generation of ROS, and exert anti-inflammatory and anti-apoptotic activity. In hind-limb I/R and liver I/R models in mice, PVAX nanoparticles specifically reacted with overproduced H2O2 and exerted highly potent anti-inflammatory and anti-apoptotic activities that reduced cellular damages. Therefore, PVAX nanoparticles have tremendous potential as nanotherapeutic agents for I/R injury and H2O2-associated diseases.en-USJournal Article2014-02-1810.1038/srep02233