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

Kang, Changsun; Cho, Wooram; Park, Minhyung; Kim, Jinsub; Park, Sanghoon; Shin, Dong–Ho; Song, Chul-Gyu; Lee, Dongwon

doi:10.1016/j.biomaterials.2016.01.070

Cited by 87 publications

(71 citation statements)

References 24 publications

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“…The ischemia-reperfusion (I/R) process occurs in many clinically important events, including hepatic resectional surgery, transplantation, trauma, and hemorrhagic shock [1–3]. Hepatic I/R injury is an inevitable complication causing severe cellular death, tissues damage, and liver dysfunction, which increases the mortality [4–6]. Reactive oxygen species (ROS), which are the main toxicants in oxidative stress, play critical roles in hepatic I/R injury [7–10].…”

Section: Introductionmentioning

confidence: 99%

“…Treatment with superoxide dismutase (SOD) and catalase (CAT) reduces the ROS levels, as SOD rapidly dismutases the superoxide (O 2 − ) to H 2 O 2 , and CAT scavenges H 2 O 2 to produce water, which reduces the severity of oxidative stress [5]. Beside SOD and CAT, a variety of compounds and biomaterials has been developed as potential therapeutic agents for I/R injury [6, 17]. However, it still lacks efficient, specific, and sensitive biomarkers for the accurate evaluation of the severity of oxidative stress in hepatic I/R injury [19].…”

Section: Introductionmentioning

confidence: 99%

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Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia-Reperfusion Injury

Guo

Liu

et al. 2016

Oxidative Medicine and Cellular Longevity

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Hepatic ischemia-reperfusion (I/R) injury is a serious complication in clinical practice. However, no efficient biomarkers are available for the evaluation of the severity of I/R injury. Recently, renalase has been reported to be implicated in the I/R injury of various organs. This protein is secreted into the blood in response to increased oxidative stress. To investigate the responsiveness of renalase to oxidative stress, we examined the changes of renalase in cell and mouse models. We observed a significant increase of renalase expression in HepG2 cells in a time- and dose-dependent manner when treated with H2O2. Renalase expression also increased significantly in liver tissues that underwent the hepatic I/R process. The increased renalase levels could be efficiently suppressed by antioxidants in vitro and in vivo. Furthermore, serum renalase levels were significantly increased in the mouse models and also efficiently suppressed by antioxidants treatment. The variation trends are consistent between renalase and liver enzymes in the mouse models. In conclusion, renalase is highly sensitive and responsive to oxidative stress in vitro and in vivo. Moreover, renalase can be detected in the blood. These properties make renalase a highly promising biomarker for the evaluation of the severity of hepatic I/R injury.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia-Reperfusion Injury

Guo

Liu

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…Therefore, incorporation of ROS‐sensitive moieties along a polymer backbone can provide accelerated polymer biodegradation kinetics. Several ROS‐sensitive polymers have been reported including poly(propylene sulfide), polythioketal, boronic ester polymers, and oxalate‐based polymers . In particular, the oxalate functional groups are degraded into carbon dioxide by H 2 O 2 , where the cyclic dioxetanedione was suggested as a reactive intermediate ( Figure ) …”

Section: Introductionmentioning

confidence: 99%

“…Oxalate‐based polymers were also used for ultrasound imaging by taking advantage of enhanced ultrasound signal intensity by the degradation products of carbon dioxide . A cancer prodrug conjugated with oxalate was designed to take advantage of the enhanced permeability and retention (EPR) as well as oxalate cleavage through increased ROS levels around cancer tissues .…”

Section: Introductionmentioning

confidence: 99%

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

Lee

Jeong

2019

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A reactive oxygen species (ROS)‐sensitive degradable polymer would be a promising material in designing a disease‐responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)–polycaprolactone–poly(ethylene glycol) (PEG–PCL–PEG or EG12–CL20–EG12) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0−37.0 wt%. In particular, the aqueous PEG–PCL–PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0–37.0 wt%, whereas the aqueous PEG–PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG–PCL–PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle‐based thermogel of PEG–PCL–PEG with ROS‐triggering degradability is a promising injectable material for biomedical applications.

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“…In particular, CO 2 bubble-generating polycarbonate nanoparticles exhibited a significantly longer imaging time than a commercial ultrasound contrast agent SonoVue and provided more anatomic landmarks in ultrasonographic imaging. In this context, there have been great efforts for the development of bubble-generating particles as ultrasound contrast agents 20.…”

Section: Introductionmentioning

confidence: 99%

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles

Kim

Kang

et al. 2017

Theranostics

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Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated diseases. Based on the notion that PVAX nanoparticles generate CO2 bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H2O2. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H2O2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.

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

Cited by 87 publications

References 24 publications

Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia-Reperfusion Injury

Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia-Reperfusion Injury

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles

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