Appl Biochem Biotechnol. 2026 Jul 16. doi: 10.1007/s12010-026-05835-2. Online ahead of print.
ABSTRACT
Oxidative stress and inflammasome-driven inflammation are key contributors to atherosclerotic disease progression. Here, we report a ROS-responsive hyaluronic acid-PEGDA hydrogel designed for the sustained delivery of palmitoleic acid. In the study, catechol-functionalized hyaluronic acid was cross-linked with polyethylene glycol diacrylate to create an extracellular matrix mimic that possessed tunable mechanical strength and redox-sensitive degradability. It showed controlled release of palmitoleic acid under normal physiological conditions and a faster rate of release under oxidative conditions. In vitro studies using vascular endothelial cells and macrophages demonstrated good cytocompatibility and a marked reduction in intracellular reactive oxygen species, lipid peroxidation, and pro-inflammatory cytokine secretion. At the molecular level, treatment with the palmitoleic acid-loaded hydrogel resulted in activation of AMP-activated protein kinase, inhibition of NF-κB nuclear translocation, and suppression of NLRP3 inflammasome activation, as evidenced by decreased caspase-1 cleavage and IL-1β maturation. These findings indicate that ROS-responsive hydrogel-mediated delivery of palmitoleic acid effectively modulates oxidative and inflammatory signalling pathways relevant to atherosclerosis.
PMID:42461343 | DOI:10.1007/s12010-026-05835-2