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 (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.
Department of BIN Fusion Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea.
Seunggyu
S
Park
Cardiovascular Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, 3 Blackfan Circle, Boston, MA 02215, USA.
Jooheung
J
Yoon
Cardiovascular Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, 3 Blackfan Circle, Boston, MA 02215, USA.
Soochan
S
Bae
Department of BIN Fusion Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea.
Minhyung
M
Park
Department of BIN Fusion Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea.
Changsun
C
Kang
Cardiovascular Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, 3 Blackfan Circle, Boston, MA 02215, USA.
Qingen
Q
Ke
Department of BIN Fusion Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea; Polymer Fusion Research Center, Department of Polymer⋅Nano Science and Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea. Electronic address: dlee@chonbuk.ac.kr.
Dongwon
D
Lee
Department of BIN Fusion Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea; Cardiovascular Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, 3 Blackfan Circle, Boston, MA 02215, USA. Electronic address: pkang@bidmc.harvard.edu.
Peter M
PM
Kang
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D001592:Benzyl Alcohols / Q000737:chemistry / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy*; D004317:Doxorubicin; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D019815:Oxalic Acid / Q000737:chemistry / Q000627:therapeutic use*; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use*
D000975:Antioxidants; D001592:Benzyl Alcohols; D011108:Polymers; D004317:Doxorubicin; D019815:Oxalic Acid; D006861:Hydrogen Peroxide; C024078:vanillyl alcohol
Anti-oxidant; Doxorubicin; Heart failure; Hydrogen peroxide; Polyoxalate