Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells

Journal article

Kermanizadeh, A., Villadsen, K., Østrem, R.G., Jensen, K.J., Møller, P. and Loft, S. 2016. Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells. Basic and Clinical Pharmacology and Toxicology. Vol 120 (Issue 4), pp. 380 - 389. https://doi.org/10.1111/bcpt.12692
AuthorsKermanizadeh, A., Villadsen, K., Østrem, R.G., Jensen, K.J., Møller, P. and Loft, S.
Abstract

Utilization of functionalized liposomes as the means of targeted delivery of therapeutics may enhance specific transport of biologically active drugs to target tissues, while avoiding or reducing undesired side effects. In the present investigation, peptide-conjugated cationic liposomes were constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells and macrophages. There was unaltered secretion of cytokines after exposure of peptide-conjugated liposomes to endothelial cells, indicating that the materials were not inflammogenic. Liposomes with a peptide targeting the fibronectin receptor (integrin α5β1) were more effective in targeting of activated endothelial cells, as compared to a liposome with a peptide that targeted both the fibronectin and vitronectin receptors, as well as liposomes with a control peptide. The liposome targeted to the fibronectin receptor also displayed uptake in endothelial cells in co-culture with activated macrophages. Therefore, this study demonstrates the feasibility of constructing a peptide-conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells.

KeywordsEndothelial Cells; Integrin Targeting; Toxicological Assessment
Year2016
JournalBasic and Clinical Pharmacology and Toxicology
Journal citationVol 120 (Issue 4), pp. 380 - 389
PublisherWiley Online Library
ISSN1742-7835
1742-7843
Digital Object Identifier (DOI)https://doi.org/10.1111/bcpt.12692
Web address (URL)http://www.scopus.com/inward/record.url?eid=2-s2.0-85008339293&partnerID=MN8TOARS
Output statusPublished
Publication dates
Online21 Oct 2016
Online12 Mar 2017
01 Apr 2017
Publication process dates
Accepted18 Oct 2016
Deposited14 Jun 2023
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