A Multifunctional Nanoplatform for Treating Hepatic Ischemia-Reperfusion Injury by Modulating the Nrf2 and NF-κB...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Hepatology

Background:

• Hepatic ischemia-reperfusion injury (HIRI) is a severe complication in liver surgeries.
• Current treatments for HIRI are limited, highlighting the need for novel therapeutic strategies.
• HIRI involves complex mechanisms including oxidative stress and immune-inflammatory responses.

Purpose of the Study:

• To develop a multifunctional nanoplatform for targeted HIRI treatment.
• To investigate the combined therapeutic effects of edaravone and dexamethasone delivered via this nanoplatform.
• To mitigate both oxidative stress and immune-mediated damage in HIRI.

Main Methods:

• Constructed an erythrocyte-membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoplatform.
• Utilized the nanoplatform for targeted delivery of edaravone (Eda) and dexamethasone (Dex).
• Investigated the modulation of nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways.

Main Results:

• The nanoplatform effectively delivered Eda and Dex to damaged hepatocytes.
• Edaravone, via the Nrf2 pathway, scavenged reactive oxygen species (ROS), reducing oxidative stress.
• Dexamethasone, via the NF-κB pathway, suppressed neutrophil-mediated inflammation.
• The strategy concurrently addressed short-term oxidative stress and long-term immune damage.

Conclusions:

• The erythrocyte-membrane-coated PLGA nanoplatform offers a targeted delivery strategy for HIRI treatment.
• This dual-action approach effectively combats both oxidative stress and immune-mediated liver injury.
• The developed nanoplatform represents a clinically promising therapeutic strategy for managing HIRI.