Targeted Sustained-Release Therapy for Vulnerable Atherosclerotic Plaques Using Luteolin-Loaded Nanoparticles

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Vulnerable atherosclerotic plaques (VAPs) pose a significant clinical challenge for precise and safe management.
• Current treatments often lack specificity, leading to potential systemic side effects.

Purpose of the Study:

• To develop and evaluate an osteopontin-targeted nanotherapeutic system (NPs-Lut) for the precise delivery and treatment of VAPs.
• To improve the bioavailability and efficacy of luteolin for treating atherosclerotic lesions.

Main Methods:

• Osteopontin-targeted nanoparticles encapsulating luteolin (NPs-Lut) were engineered.
• In vitro sustained-release and in vitro/in vivo biosafety evaluations were performed.
• Therapeutic efficacy was assessed in ApoE-/- mice models of atherosclerosis.

Main Results:

• NPs-Lut demonstrated superior performance compared to atorvastatin nanoparticles (NPs-AST) in reducing plaque inflammation, endoplasmic reticulum stress, and foam cell apoptosis.
• Significant improvements in plaque stability were observed, including reduced necrotic core area and increased fibrous cap thickness.
• NPs-Lut enhanced luteolin's solubility and bioavailability, achieving potent therapeutic effects at low doses with minimal systemic toxicity.

Conclusions:

• The developed nanoplatform offers a robust and translationally promising strategy for the precision treatment of VAPs.
• This approach provides a novel, safe, and effective intervention for atherosclerotic cardiovascular disease.