Target-Engineered Liposomes Decorated with Nanozymes Alleviate Liver Fibrosis by Remodeling the Liver...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Hepatology

Background:

• Liver fibrosis results from sustained liver injury, involving reactive oxygen species (ROS) and activated hepatic stellate cells (HSCs).
• Liver macrophages exacerbate fibrosis through ROS production and pro-inflammatory signaling, creating a detrimental hepatic microenvironment.

Purpose of the Study:

• To develop a targeted nanomedicine, HCOL, for mitigating liver fibrosis.
• To investigate HCOL's efficacy in scavenging ROS, alleviating hypoxia, and modulating macrophage polarization in fibrotic liver models.

Main Methods:

• Development of cerium oxide nanozymes templated by hyaluronic acid (HA) and surface-decorated on oleanolic acid (OA)-loaded liposomes (HCOL).
• Evaluation of HCOL's antioxidant properties, including superoxide dismutase (SOD) and catalase (CAT) activities.
• Assessment of HCOL's impact on ROS levels, macrophage polarization (M1 to M2 shift), and interleukin 10 (IL-10) production in vitro and in vivo models of liver fibrosis.

Main Results:

• HCOL demonstrated significant ROS scavenging capabilities in HSCs and macrophages.
• HCOL treatment promoted a shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages, increasing IL-10 production.
• The nanozyme formulation effectively alleviated hypoxia and reduced the inflammatory microenvironment associated with liver fibrosis.

Conclusions:

• HCOL represents a potent nanotherapeutic agent for liver fibrosis by targeting ROS and inflammation.
• The dual action of antioxidant and anti-inflammatory effects makes HCOL a promising strategy for decelerating liver fibrosis progression.