Oxidation-responsive PEG-poly(α-lipoic acid) nanoparticles for coenzyme Q10 delivery attenuate hepatic ischemia-reperfusion injury via ROS scavenging and ferroptosis inhibition

Abstract

Hepatic ischemia-reperfusion injury (IRI) is characterized by an acute surge of reactive oxygen species (ROS) upon reperfusion, leading to oxidative damage and cell death. Ferroptosis, a form of iron-dependent lipid peroxidation-driven cell death, has recently been implicated in hepatic IRI, compounding the injury. Here, we present an oxidation-responsive nanoparticle system designed to mitigate liver IRI by scavenging ROS and inhibiting ferroptosis. We synthesized a PEGylated poly(α-lipoic acid) (PEG-PαLA) copolymer that self-assembles into nanoparticles encapsulating the lipophilic antioxidant coenzyme Q10 (CoQ10). The PEG-PαLA/CoQ10 nanoparticles have an average diameter of ~100 nm and release CoQ10 preferentially under oxidative conditions. In vitro, the nanoparticles efficiently neutralized free radicals and protected hepatocytes from oxidative injury. In a mouse model of partial hepatic IRI, treatment with PEG-PαLA/CoQ10 nanoparticles significantly reduced liver injury markers, preserved liver histology, and abrogated lipid peroxidation, indicating suppression of ferroptosis. Our results demonstrated that PEG-PαLA/CoQ10 nanoparticle is a novel antioxidant nanomedicine that synergistically attenuates ROS-mediated damage and ferroptotic cell death in hepatic IRI. These findings highlight a promising strategy for protecting organs from ischemia-reperfusion damage by targeting oxidative stress and ferroptosis with responsive biomaterial carriers.

Article information

Article type
Paper
Submitted
10 May 2025
Accepted
05 Jun 2025
First published
06 Jun 2025

J. Mater. Chem. B, 2025, Accepted Manuscript

Oxidation-responsive PEG-poly(α-lipoic acid) nanoparticles for coenzyme Q10 delivery attenuate hepatic ischemia-reperfusion injury via ROS scavenging and ferroptosis inhibition

Y. Guan, J. Liu, J. Yang, S. Chen, W. Yao, S. Gong, C. Xiao, M. Li, G. Luo and Z. Hei, J. Mater. Chem. B, 2025, Accepted Manuscript , DOI: 10.1039/D5TB01118C

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