Inflammation-targeted nanoparticles modulate macrophage polarization for coronary therapy in Kawasaki disease

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Kawasaki disease (KD) causes coronary artery lesions due to oxidative stress and M1 macrophage inflammation.
• Current treatments face challenges in targeting the inflamed microenvironment.
• Modulating macrophage polarization from M1 to M2 is a potential therapeutic strategy.

Purpose of the Study:

• To develop a reactive oxygen species (ROS)-responsive nanoplatform for targeted simvastatin delivery in KD.
• To investigate the nanoplatform's ability to reduce oxidative stress and promote anti-inflammatory macrophage polarization.
• To evaluate the therapeutic efficacy of the nanoplatform in a KD mouse model.

Main Methods:

• Development of a hyaluronic acid (HA)-decorated, ROS-responsive nanocarrier (HA-Sim@BRPL) using poly-l-lysine conjugated with bilirubin (BR).
• ROS-triggered release of simvastatin (Sim) via bilirubin's oxidation to biliverdin.
• In vitro assessment of ROS reduction, macrophage polarization, and endothelial cell survival.
• In vivo evaluation in a KD mouse model, assessing coronary artery lesions and cardiac function.

Main Results:

• HA-Sim@BRPL demonstrated targeted delivery to macrophages via CD44 interaction.
• The nanoplatform effectively reduced intracellular ROS and promoted M2 macrophage polarization.
• Treatment with HA-Sim@BRPL significantly attenuated coronary artery lesions and improved cardiac function in KD mice.
• Enhanced endothelial cell survival was observed through intercellular signaling.

Conclusions:

• The developed HA-Sim@BRPL nanomedicine offers a promising therapeutic strategy for KD coronary complications.
• This approach effectively integrates oxidative stress responsiveness and targeted inflammatory cell modulation.
• The nanoplatform shows potential for treating vascular inflammation and injury in KD.