One Stone, Four Birds: Multiple Modulation of Infarct Microenvironment-Based ROS-Responsive Hydrogel for Cardiac...

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Drug Delivery Systems

Background:

• Myocardial infarction (MI) presents significant global health challenges with limited effective treatments.
• Current strategies targeting single cell types in MI pathology are insufficient due to the involvement of multiple cell types like fibroblasts, cardiomyocytes, immune cells, and endothelial cells.

Purpose of the Study:

• To develop a ROS-responsive delivery system for microRNA-21 (miR-21) and DB1976 (a PU.1 inhibitor) to comprehensively remodel the cardiac microenvironment post-MI.
• To investigate the combined therapeutic effects of miR-21 and DB1976 in a mouse model of myocardial infarction.

Main Methods:

• Development of a mesoporous silica nanoparticle (MSN)-based hydrogel encapsulating miR-21 and DB1976.
• Utilized a ROS-responsive system for targeted delivery.
• Evaluated the hydrogel's efficacy in a mouse MI model, assessing cardiac function and cellular remodeling.

Main Results:

• The developed MSN/miR-21-DB hydrogel demonstrated significant improvement in cardiac function in a mouse MI model.
• The system effectively remodeled multiple cardiac cell types, including cardiomyocytes, macrophages, fibroblasts, and vascular endothelial cells.
• Combined delivery of miR-21 and DB1976 synergistically addressed angiogenesis, apoptosis, inflammation, and fibrosis.

Conclusions:

• This novel dual-delivery system offers a promising strategy for cardiac repair after myocardial infarction.
• Simultaneously regulating multiple cell types within the cardiac microenvironment represents a more comprehensive therapeutic approach for damaged heart tissue.