Phage-display-guided nanocarrier targeting to atheroprone vasculature

ACS Nano
Lucas H HofmeisterHak-Joon Sung

Abstract

In regions of the circulation where vessels are straight and unbranched, blood flow is laminar and unidirectional. In contrast, at sites of curvature, branch points, and regions distal to stenoses, blood flow becomes disturbed. Atherosclerosis preferentially develops in these regions of disturbed blood flow. Current therapies for atherosclerosis are systemic and may not sufficiently target these atheroprone regions. In this study, we sought to leverage the alterations on the luminal surface of endothelial cells caused by this atheroprone flow for nanocarrier targeting. In vivo phage display was used to discover unique peptides that selectively bind to atheroprone regions in the mouse partial carotid artery ligation model. The peptide GSPREYTSYMPH (PREY) was found to bind 4.5-fold more avidly to the region of disturbed flow and was used to form targeted liposomes. When administered intravenously, PREY-targeted liposomes preferentially accumulated in endothelial cells in the partially occluded carotid artery and other areas of disturbed flow. Proteomic analysis and immunoblotting indicated that fibronectin and Filamin-A were preferentially bound by PREY nanocarriers in vessels with disturbed flow. In additional experiments, PREY ...Continue Reading

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Citations

Feb 26, 2016·Nanomedicine·Mahdi KarimiMichael R Hamblin
Oct 31, 2016·Advanced Drug Delivery Reviews·Mahdi KarimiMichael R Hamblin
Feb 24, 2018·Nanomedicine·Mario D MartinezMichael E Davis
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Apr 13, 2021·International Journal of Peptide Research and Therapeutics·Shuhui ZhaoJianfang Zhang
Jun 12, 2018·Bioconjugate Chemistry·Maureen R Newman, Danielle S W Benoit
Nov 12, 2018·ACS Biomaterials Science & Engineering·Dae-Hyun KimHak-Joon Sung

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