Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Atherosclerosis is a leading global cause of death due to challenges in early detection.
• Macrophage apoptosis significantly contributes to atherosclerotic lesion instability.
• Targeted nanoparticles offer a promising strategy for early plaque detection and intervention.

Purpose of the Study:

• To construct a synthetic, biodegradable high-density lipoprotein (HDL)-mimicking nanoparticle (NP) platform.
• To enable early detection of vulnerable atherosclerotic plaques by targeting mitochondrial membrane potential collapse during apoptosis.
• To explore the therapeutic potential of HDL mimics in atherosclerosis management.

Main Methods:

• Synthesized biodegradable HDL-mimicking NPs using poly(lactic-co-glycolic acid), cholesteryl oleate, and a phospholipid bilayer.
• Decorated NPs with triphenylphosphonium (TPP) cations for apoptosis detection and apolipoprotein A-I mimetic 4F peptide.
• Incorporated quantum dots (QDs) for optical imaging and conducted in vitro and in vivo studies.

Main Results:

• In vitro studies demonstrated promising detection of apoptosis and cholesterol binding capabilities.
• The NPs showed potential for reverse cholesterol transport.
• In vivo studies in rats revealed favorable biodistribution, controlled pharmacokinetics, and significant triglyceride reduction.

Conclusions:

• The developed TPP-HDL-apoA-I-QD NPs exhibit excellent biocompatibility, stability, and are non-toxic and non-immunogenic.
• These NPs show significant promise for early plaque diagnosis in atherosclerosis.
• Potential applications include preventing vulnerable plaque progression and initiating preventative therapies.