Therapeutic use of H2O2-responsive anti-oxidant polymer nanoparticles for doxorubicin-induced cardiomyopathy.

Abstract Doxorubicin (DOX) is a commonly used anti-neoplastic agent but its clinical use is limited due to serious hepatic and cardiac side effects. DOX-induced toxicity is mainly associated with overproduction of reactive species oxygen (ROS) such as hydrogen peroxide (H 2 O 2 ). We have recently developed H 2 O 2 -responsive anti-oxidant polymer, polyoxalate containing vanillyl alcohol (PVAX), which is designed to rapidly scavenge H 2 O 2 and release vanillyl alcohol with anti-oxidant, anti-inflammatory and anti-apoptotic properties. In this study, we report that PVAX nanoparticles are novel therapeutic agents for treating DOX-induced cardiac and hepatic toxicity. Intraperitoneal injection of PVAX nanoparticles (4 mg/kg/day) resulted in significant inhibition in apoptosis in liver and heart of DOX-treated mice by suppressing the activation of poly (ADP ribose) polymerase 1 (PARP-1) and caspase-3. PVAX treatment also prevented DOX-induced cardiac dysfunction. Furthermore, survival rate (vehicle = 35% vs . PVAX = 75%; p