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Published Online: 17 January 2022

Self-Assembling Antioxidants for Ischemia–Reperfusion Injuries

Publication: Antioxidants & Redox Signaling
Volume 36, Issue Number 1-3


Significance: Ischemia–reperfusion (IR) injury is a major component of severe damage in vascular occlusion during stroke, myocardial infarction, surgery, and organ transplantation, and is exacerbated by the excessive generation of reactive oxygen species (ROS), which occurs particularly during reperfusion. With the aging of the population, IR injury is becoming a serious problem in various organs, such as the kidney, brain, and heart, as well as in the mesenteric capillaries.
Recent Advances: To prevent reperfusion injuries, natural and synthetic low-molecular-weight (LMW) antioxidants have been well studied.
Critical Issues: However, these LMW antioxidants have various problems, including adverse effects due to excessive cellular uptake and their rapid clearance by the kidney, and cannot fully exert their potent antioxidant capacity in vivo.
Future Directions: To overcome these problems, we designed and developed redox polymers with antioxidants covalently conjugated with them. These polymers self-assemble into nanoparticles in aqueous media, referred to as redox nanoparticles (RNPs). RNPs suppress their uptake into normal cells, accumulate at inflammation sites, and effectively scavenge ROS in damaged tissues. We had developed two types of RNPs: RNPN, which disintegrates in response to acidic pH; and RNPO, which does not collapse, regardless of the environmental pH. Utilizing the pH-sensitive and -insensitive characteristics of RNPN and RNPO, respectively, RNPs were found to exhibit remarkable therapeutic effects on various oxidative stress disorders, including IR injuries. Thus, RNPs are promising nanomedicines for use as next-generation antioxidants. This review summarizes the therapeutic impacts of RNPs in the treatment of kidney, cerebral, myocardial, and intestinal IR injuries. Antioxid. Redox Signal. 36, 70–80.

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Information & Authors


Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 36Issue Number 1-3January 2022
Pages: 70 - 80
PubMed: 34074133


Published online: 17 January 2022
Published in print: January 2022
Published ahead of print: 7 September 2021
Published ahead of production: 2 June 2021
Accepted: 15 May 2021
Received: 13 May 2021


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Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan.
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan.
Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Center for Research in Isotopes and Environmental Dynamics (CRiED), University of Tsukuba, Tsukuba, Japan.


Address correspondence to: Prof. Yukio Nagasaki, Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Japan [email protected]

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No competing financial interests exist.

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We have no funding for this review article. We usually appreciate the fundings for original contribution.

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