Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Nanotechnology

Background:

• Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is linked to atherosclerosis and expressed in vascular smooth muscle cells (VSMCs).
• PCSK9-mediated VSMC phenotypic transformation, proliferation, and migration accelerate atherosclerosis progression.

Purpose of the Study:

• To design a biomimetic nanoliposome loaded with Evolocumab (Evol), a PCSK9 inhibitor, for atherosclerosis treatment.
• To evaluate the efficacy of these nanoparticles in inhibiting VSMC abnormalities and reducing PCSK9 expression.

Main Methods:

• Development of biomimetic nanoliposomes encapsulating Evolocumab ((Lipo+M)@E NPs).
• In vitro assessment of nanoparticle effects on VSMC markers (α-SMA, Vimentin, OPN) and functions.
• In vivo evaluation in ApoE-/- mice to measure serum and plaque PCSK9 levels and nanoparticle performance (circulation, targeting, accumulation).

Main Results:

• In vitro studies demonstrated that (Lipo+M)@E NPs inhibited VSMC phenotypic transition, proliferation, and migration by modulating key protein expressions.
• In vivo studies showed that (Lipo+M)@E NPs exhibited long circulation, excellent targeting, and accumulation in atherosclerotic plaques.
• Significant reduction in serum and VSMC PCSK9 expression within plaques was observed in treated ApoE-/- mice.

Conclusions:

• Biomimetic nanoliposomes loaded with Evolocumab represent a promising strategy for alleviating atherosclerosis.
• The developed nanoparticles effectively target atherosclerotic lesions and inhibit PCSK9-driven VSMC dysfunction.
• This nanodrug delivery system offers potential for improved atherosclerosis management.