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

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 (H₂O₂). We have recently developed H₂O₂-responsive anti-oxidant polymer, polyoxalate containing vanillyl alcohol (PVAX), which is designed to rapidly scavenge H₂O₂ 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 (4mg/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<0.05) was significantly improved in a PVAX nanoparticles-treated group compared with vehicle treated groups. Taken together, we anticipate that PVAX nanoparticles could be a highly specific and potent treatment modality in DOX-induced cardiac and hepatic toxicity.