title: H2O2-responsive molecularly engineered polymer nanoparticles as ischemia/reperfusion-targeted nanotherapeutic agents.
abstract: The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the most abundant form of ROS produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. Here, we report H2O2-responsive antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA) (PVAX) as a novel I/R-targeted nanotherapeutic agent. PVAX was designed to incorporate VA and H2O2-responsive peroxalate ester linkages covalently in its backbone. PVAX nanoparticles therefore degrade and release VA, which is able to reduce the generation of ROS, and exert anti-inflammatory and anti-apoptotic activity. In hind-limb I/R and liver I/R models in mice, PVAX nanoparticles specifically reacted with overproduced H2O2 and exerted highly potent anti-inflammatory and anti-apoptotic activities that reduced cellular damages. Therefore, PVAX nanoparticles have tremendous potential as nanotherapeutic agents for I/R injury and H2O2-associated diseases.
authors.affiliation: WCU Department of BIN Fusion Technology, Chonbuk National University, Dukjin 664-14, Jeonju, Chonbuk 561-756, South Korea.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
authors.forename: Soochan
authors.initials: S
authors.lastname: Bae
authors.forename: Donghyun
authors.initials: D
authors.lastname: Hong
authors.forename: Hyungsuk
authors.initials: H
authors.lastname: Lim
authors.forename: Joo Heung
authors.initials: JH
authors.lastname: Yoon
authors.forename: On
authors.initials: O
authors.lastname: Hwang
authors.forename: Seunggyu
authors.initials: S
authors.lastname: Park
authors.forename: Qingen
authors.initials: Q
authors.lastname: Ke
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis; D001592:Benzyl Alcohols / Q000737:chemistry; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001592:Benzyl Alcohols; D011108:Polymers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C024078:vanillyl alcohol