uPAR-Guided Dendrimer Gel Nanoparticles Reprogram Inflammation to Stabilize Atherosclerotic Plaques

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cardiovascular Research

Background:

• Atherosclerosis involves lipid deposition, inflammation, and apoptosis, with residual risk remaining after lipid-lowering therapies.
• Current treatments do not fully address local inflammation and cell death contributing to cardiovascular risk.

Purpose of the Study:

• To develop targeted nanoparticles (G5PM-uPA/RA) for atherosclerosis therapy.
• To utilize urokinase plasminogen activator (uPA) functionalization for targeting uPAR-enriched plaques.

Main Methods:

• Dendrimer nanoparticles (G5PM-uPA/RA) were synthesized using flash nanoprecipitation and uPA conjugation.
• In vitro studies assessed macrophage uptake, drug retention, and cytokine release.
• In vivo studies in Ldlr-/- mice evaluated biodistribution, plaque burden, and safety.

Main Results:

• G5PM-uPA/RA showed enhanced macrophage uptake and sustained intracellular drug retention.
• In vivo treatment significantly reduced plaque burden, necrotic core size, inflammation, and apoptosis.
• Therapy promoted fibrous cap thickening without observed systemic toxicity.

Conclusions:

• G5PM-uPA/RA nanoparticles effectively target atherosclerotic lesions.
• This approach modulates inflammation and stabilizes plaques, offering a safe nanomedicine strategy for atherosclerosis.