Co-Targeting Biomimetic Nanoparticles Alleviate Atherosclerosis by Inhibiting the Vicious Circle Between Inflammation...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cardiovascular Research

Background:

• Atherosclerosis (AS) involves LDL accumulation and oxidation, leading to endothelial cell (EC) dysfunction and pro-inflammatory macrophage (M1) polarization.
• This cascade exacerbates inflammation and lipid buildup, creating a vicious cycle detrimental to cardiovascular health.
• A dual-targeting strategy addressing both ECs and macrophages is crucial for effective AS intervention.

Purpose of the Study:

• To develop and evaluate dual-targeting biomimetic nanoparticles for atherosclerosis treatment.
• To investigate the efficacy of simvastatin-loaded nanomicelles coated with platelet membrane (PM@PLA-PEG/SIM) in inhibiting the inflammation-lipid cycle in AS.
• To assess the therapeutic potential of PM@PLA-PEG/SIM in preclinical models of AS.

Main Methods:

• Simvastatin (SIM) was loaded into PLA-PEG nanomicelles, then coated with platelet membrane (PM) to create PM@PLA-PEG/SIM nanoparticles.
• Nanoparticle characterization included TEM for morphology, CCK-8 assay and live/dead staining for cytotoxicity.
• In vitro and in vivo studies utilized flow cytometry, CLSM, and ApoE-/- mouse models to assess targeting, biosafety, and therapeutic efficacy.

Main Results:

• PM@PLA-PEG/SIM nanoparticles demonstrated reduced simvastatin toxicity and good biocompatibility.
• In vitro, nanoparticles inhibited foam cell formation and modulated cytokine expression (decreased IL-6, increased IL-4, IL-10) by promoting macrophage repolarization.
• In vivo, PM@PLA-PEG/SIM exhibited excellent plaque targeting, significantly reducing plaque area, lipid levels, and improving plaque stability in AS mouse models.

Conclusions:

• PM@PLA-PEG/SIM nanoparticles effectively alleviate atherosclerosis progression by co-targeting endothelial cells and macrophages.
• This dual-targeting approach successfully inhibits the detrimental cycle of inflammation and lipid accumulation in AS.
• The developed biomimetic nanoparticles represent a novel and promising therapeutic strategy for atherosclerosis treatment.