Key result
Novel organic-core HDL nanoparticle variant shows superior cholesterol efflux and anti-inflammatory capacity in vitro.
Tuning the core composition and phospholipids of synthetic HDL nanoparticles can optimize their cholesterol efflux and anti-inflammatory properties in vitro.
High-density lipoprotein (HDL) cholesterol (HDL-C) levels have been associated with risk of atherosclerotic cardiovascular disease (ASCVD). Therapeutic interventions aimed at increasing HDL-C have largely failed to produce patient benefits in clinical trials. Thus, there has been a shift away from targeting HDL-C and a focus on better understanding HDL structure–function relationships. Because of the heterogeneity of natural HDLs, HDL mimetics with defined physicochemical properties provide a useful tool to study HDL function(s). Here, we report the design and in vitro characterization of spherical HDL-like nanoparticles (HDL NPs) incorporating organic core (oc) scaffolds to investigate how core composition and phospholipids influence HDL NP function. We synthesized six unique spherical oc-HDL NPs and confirmed the formation of nanoparticles ∼10–15 nm in diameter and with physical features consistent with native HDL. We identified an oc-HDL NP that exhibited superior cholesterol efflux capacity and anti-inflammatory function, providing insights into engineering HDL mimetics as effective therapies.
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Trujillo et al. (2026) studied this question. Spherical HDL-like nanoparticles incorporating organic core scaffolds was evaluated on Cholesterol efflux capacity and anti-inflammatory function. Synthesis of six unique spherical organic core HDL-like nanoparticles identified one variant with superior in vitro cholesterol efflux capacity and anti-inflammatory function.
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