Excessive inflammatory response during sepsis causes irreversible damage to healthy tissues and results in multi-organ failure. During infection, bacterial endotoxin-triggered inflammatory responses in macrophages facilitate the recruitment of circulating leukocytes, including neutrophils and monocytes. A key component that aggravates the systemic inflammatory response is the generation of stable reactive oxygen species like hydrogen peroxide (H2O2). In this study, we present a versatile strategy for reducing the activation of tissue-resident macrophages and preventing leukocyte infiltration in an LPS-induced endotoxemia model. We designed and synthesized hyaluronic acid stabilized Prussian blue (HAPB) nanoparticles and validated their activity in the dismutation of H2O2 in LPS-induced tissue-resident macrophages. Hyaluronic acid provided stability and enhanced intracellular uptake of insoluble Prussian blue through the CD44 receptor in the LPS-activated macrophages. Following HAPB administration in an LPS-induced peritonitis murine model, the level of M1 inflammatory macrophage population decreased, and infiltration of neutrophils along with monocytes was suppressed. Overall, we have developed biocompatible Prussian blue nanoparticles that can mitigate inflammatory stress LPS-induced endotoxemia by scavenging the intracellular peroxide production, thereby inhibiting inflammatory cascades in tissue-resident macrophages. Therefore, HAPB nanoparticles may potentially be used as novel nano-stress relievers for sepsis. The nanomaterial may have clinical applicability in sepsis and in other inflammatory diseases involving peroxides as key inflammatory agents.

Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.