Therapeutic use of H2O2-responsive anti-oxidant polymer nanoparticles for doxorubicin-induced cardiomyopathy.
Biomaterials
; 35(22): 5944-53, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24767791
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 (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 (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 < 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Polímeros
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Ácido Oxálico
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Peróxido de Hidrogênio
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Cardiomiopatias
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Antioxidantes
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article