Nanoparticle-based "Two-pronged" approach to regress atherosclerosis by simultaneous modulation of cholesterol influx and efflux. Biomaterials 2020 Nov;260:120333
Date
08/28/2020Pubmed ID
32853832Pubmed Central ID
PMC7530139DOI
10.1016/j.biomaterials.2020.120333Scopus ID
2-s2.0-85089733138 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
Reduction of lipoprotein uptake by macrophages and stimulation of cholesterol efflux are two essential steps required for atherosclerotic plaque regression. We used the optimized mannose-functionalized dendrimeric nanoparticle (mDNP)-based platform for macrophage-specific delivery of therapeutics to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR ligand (LXR-L, to stimulate cholesterol efflux) - a novel "Two-pronged" approach to facilitate plaque regression. mDNP-mediated delivery of SR-A siRNA led to a significant reduction in SR-A expression with a corresponding decrease in uptake of oxLDL. Delivery of LXR-L increased expression of ABCA1/G1 and cholesterol efflux. Combined delivery of siRNA and LXR-L led to a significantly greater decrease in macrophage cholesterol content compared to either treatment alone. Administration of this in vitro optimized formulation of mDNP complexed with SR-A-siRNA and LXR-L (Two-pronged complex) to atherosclerotic LDLR-/- mice fed western diet (TD88137) led to significant regression of atherosclerotic plaques with a corresponding decrease in aortic cholesterol content.
Author List
He H, Wang J, Yannie PJ, Korzun WJ, Yang H, Ghosh SAuthor
Hu Yang PhD Chair, Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ATP Binding Cassette Transporter 1Animals
Atherosclerosis
Cholesterol
Liver X Receptors
Mice
Mice, Knockout
Nanoparticles
