title: H2O2-responsive antioxidant polymeric nanoparticles as therapeutic agents for peripheral arterial disease.
abstract: Peripheral artery disease (PAD) is a common circulatory disorder in which narrowed arteries limit blood flow to the lower extremity and affect millions of people worldwide. Therapeutic angiogenesis has emerged as a promising strategy to treat PAD patients because surgical intervention has been showing limited success. Leg muscles of PAD patients have significantly high level of ROS (reactive oxygen species) and the increased production of ROS is a key mechanism of initiation and progression of PAD. We have recently developed H2O2-responsive polymer PVAX, which is designed to rapidly scavenge H2O2 and release vanillyl alcohol with antioxidant and anti-inflammatory activity. In this study, we investigated the therapeutic efficacy of PVAX nanoparticles for PAD using a cell culture model and a mouse model of hindlimb ischemia. PVAX nanoparticles significantly enhanced the expression of angiogenic inducers such as vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (PECAM)-1 in human umbilical vein endothelial cells (HUVEC). PVAX nanoparticles promoted revascularization and restoration of blood perfusion into ischemic tissues by upregulating angiogenic VEGF and PECAM-1. This work demonstrates that H2O2-responsive PVAX nanoparticles facilitate therapeutic angiogenesis and hold tremendous translational potential as therapeutic systems for ischemic diseases such as PAD.
authors: Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, South Korea.
authors: Byeongsu
authors: B
authors: Kwon
authors: Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, South Korea.
authors: Changsun
authors: C
authors: Kang
authors: Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, South Korea.
authors: Jinsub
authors: J
authors: Kim
authors: Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, South Korea.
authors: Donghyuck
authors: D
authors: Yoo
authors: Division of Cardiology, Department of Internal Medicine, College of Medicine, Kangwon National University, Chuncheon, Kangwon, 200-701, South Korea.
authors: Byung-Ryul
authors: BR
authors: Cho
authors: Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors: Peter M
authors: PM
authors: Kang
authors: Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, South Korea; Department of Polymer·Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, South Korea. Electronic address: dlee@chonbuk.ac.kr.
authors: Dongwon
authors: D
authors: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011108:Polymers / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011108:Polymers; D006861:Hydrogen Peroxide
keywords: Angiogenesis; Hydrogen peroxide; Ischemia; Nanoparticles; Peripheral artery disease