Conformationally Variable Peptides Trap and Detoxify Ox-LDL in Plaques for Attenuating Atherosclerosis in Multiple...

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Nanomedicine

Background:

• Atherosclerosis (AS) poses a significant global health burden, driven by lipid deposition, inflammation, and endothelial dysfunction.
• Current therapies struggle to address these multiple pathological aspects concurrently.
• Oxidized low-density lipoproteins (ox-LDL) are key contributors to AS pathogenesis.

Purpose of the Study:

• To develop a novel nanoparticle, Rapa@BIFD, for targeted, multitarget therapy of atherosclerosis.
• To evaluate the efficacy and safety of Rapa@BIFD in preclinical AS models.
• To combine the plaque-targeting capabilities of BIFD with the anti-inflammatory action of rapamycin (Rapa).

Main Methods:

• Development of BIFD, a peptide targeting lysophosphatidylcholine (LPC) on ox-LDL, forming nanoaggregates.
• Encapsulation of rapamycin (Rapa) into BIFD to create Rapa@BIFD nanoparticles (NPs).
• In vitro and in vivo studies using apolipoprotein E-knockout murine and canine models of AS.

Main Results:

• Rapa@BIFD effectively targeted AS plaques, reducing oxidative damage and inflammation.
• The nanoparticles promoted lipid metabolism and excretion in macrophages.
• Rapa@BIFD demonstrated reduced side effects compared to rapamycin alone, including mitigated hyperlipidemia and splenic toxicity.

Conclusions:

• Rapa@BIFD represents a transformative multitarget therapeutic strategy for atherosclerosis.
• This approach combines high efficacy with minimal side effects, enhancing clinical translatability.
• Targeted nanoparticle delivery offers a promising avenue for managing complex diseases like AS.