期刊
NANOSCALE
卷 12, 期 17, 页码 9541-9556出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nr00308e
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- National Institute of General Medical Sciences, National Institutes of Health [R01GM072667]
- Michigan State University
Atherosclerosis is associated with inflammation in the arteries, which is a major cause of heart attacks and strokes. Reducing the extent of local inflammation at atherosclerotic plaques can be an attractive strategy to combat atherosclerosis. While statins can exhibit direct anti-inflammatory activities, the high dose required for such a therapy renders it unrealistic due to their low systemic bioavailabilities and potential side effects. To overcome this, a new hyaluronan (HA)-atorvastatin (ATV) conjugate was designed with the hydrophobic statin ATV forming the core of the nanoparticle (HA-ATV-NP). The HA on the NPs can selectively bind with CD44, a cell surface receptor overexpressed on cells residing in atherosclerotic plaques and known to play important roles in plaque development. HA-ATV-NPs exhibited significantly higher anti-inflammatory effects on macrophages compared to ATV alone in vitro. Furthermore, when administered in an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis following a 1-week treatment regimen, HA-ATV-NPs markedly decreased inflammation in advanced atherosclerotic plaques, which were monitored through contrast agent aided magnetic resonance imaging. These results suggest CD44 targeting with HA-ATV-NPs is an attractive strategy to reduce harmful inflammation in atherosclerotic plaques.
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