Gold Nanoparticles Coated with High Density Lipoprotein Enable Both Simultaneous Detection and Therapy of Macrophage-rich Plaques in Animal Models

Background: Identification and treatment of inflamed, unstable atherosclerotic lesions is challenging. Recent studies have shown that gold nanoparticles (GNPs) are uptaken by macrophages, and that high density lipoprotein (HDL) attenuates atherosclerotic vascular disease by exerting anti-inflammatory effects including inhibition of lipoprotein-associated phospholipase A2 (Lp-PLA2).

Objectives: We aimed to use GNPs coupled with HDL to enable both detection and treatment targeted directly to macrophage-rich atherosclerotic plaques.

Methods: In vitro: human macrophage cell culture was incubated with GNPs that were coated with HDL. GNPs-HDL uptake and Lp-PLA2 levels were measured. In vivo study was performed on both rat carotid artery balloon injury model and hyperlipidemic mice. Two weeks after rats were exposed to carotid injury, and 12 weeks after mice were exposed to high cholesterol diet, GNPs or GNPs-HDL were injected. Diffusion-reflection (DR) measurement was taken 24 hours later, and injured arteries were CT imaged and pathologically tested after two weeks.

Results: In vitro experiments showed that macrophages uptake the GNPs-HDL particles, and that GNPs-HDL were associated with lower Lp-PLA2 levels in culture media than GNPs alone. In the in vivo models, the DR method clearly detected accumulation of both, GNPs and GNPs-HDL nanoparticles in the injured arteries after 24 hours. Two weeks following the GNPs-HDL injection the amount of inflammatory cells in the neointima was significantly lower compared to GNPs without HDL. Furthermore, HDL treatment caused a reduction in macrophage accumulation in the injured artery, as demonstrated by both high resolution CT images and by histology immunostaining with macrophages cell marker CD68.

Conclusions: Application of this unique method based on GNPs-HDL presents a potential tool for the simultaneous detection and targeted treatment of atherosclerotic macrophage-rich unstable plaques.

Key words: atherosclerosis, nanoparticle, nanotechnology, HDL particle size