H₂O₂-triggered bubble generating antioxidant polymeric nanoparticles as ischemia/reperfusion targeted nanotheranostics

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• 作者：Changsun Kang^a ; Wooram Cho^a ; Minhyung Park^a ; Jinsub Kim^a ; Sanghoon Park^b ; Dongho Shin^b ; Chulgyu Song^b ; Dongwon Lee^a ; ^c ; ^{dlee@chonbuk.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ultrasound imaging ; Hydrogen peroxide ; Polymer ; Ischemia/reperfusion ; Theranostic
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：85
• 期：Complete
• 页码：195-203
• 全文大小：3010 K

文摘

Overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂) leads to oxidative stress, causing inflammation and cellular damages and death. H₂O₂ is one of the most stable and abundant ROS and H₂O₂-mediated oxidative stress is considered as a key mediator of cellular and tissue damages during ischemia/reperfusion (I/R) injury. Therefore, H₂O₂ could hold tremendous potential as a diagnostic biomarker and therapeutic target for oxidative stress-associated inflammatory conditions such as I/R injury. Here, we report a novel nanotheranostic agent that can express ultrasound imaging and simultaneous therapeutic effects for hepatic I/R treatment, which is based on H₂O₂-triggered CO₂-generating antioxidant poly(vanillin oxalate) (PVO). PVO nanoparticles generate CO₂ through H₂O₂-triggered oxidation of peroxalate esters and release vanillin, which exerts antioxidant and anti-inflammatory activities. PVO nanoparticles intravenously administrated remarkably enhanced the ultrasound signal in the site of hepatic I/R injury and also effectively suppressed the liver damages by inhibiting inflammation and apoptosis. To our best understanding, H₂O₂-responsive PVO is the first platform which generates bubbles to serve as ultrasound contrast agents and also exerts therapeutic activities. We therefore anticipate that H₂O₂-triggered bubble-generating antioxidant PVO nanoparticles have great potential for ultrasound imaging and therapy of H₂O₂-associated diseases.