Synthetic hydrogel nanoparticles for sepsis therapy

Hiroyuki Koide (), Anna Okishima, Yu Hoshino (), Yuri Kamon, Keiichi Yoshimatsu, Kazuhiro Saito, Ikumi Yamauchi, Saki Ariizumi, Yuqi Zhou, Ting-Hui Xiao, Keisuke Goda, Naoto Oku, Tomohiro Asai and Kenneth J. Shea ()
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Hiroyuki Koide: University of Shizuoka
Anna Okishima: University of Shizuoka
Yu Hoshino: Kyushu University
Yuri Kamon: University of California Irvine
Keiichi Yoshimatsu: University of California Irvine
Kazuhiro Saito: University of Shizuoka
Ikumi Yamauchi: University of Shizuoka
Saki Ariizumi: University of Shizuoka
Yuqi Zhou: The University of Tokyo
Ting-Hui Xiao: The University of Tokyo
Keisuke Goda: The University of Tokyo
Naoto Oku: University of Shizuoka
Tomohiro Asai: University of Shizuoka
Kenneth J. Shea: University of California Irvine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protects mice against a lethal dose of histones through the inhibition of platelet aggregation and migration into the lungs. In vivo administration in murine sepsis model mice results in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis therapy and adds to our understanding of the importance of histones to this condition.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25847-2

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DOI: 10.1038/s41467-021-25847-2

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