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, Kenneth J. Shea

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number5552
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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