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

Ali Kermanizadeh, Klaus Villadsen, Ragnhild G. Østrem, Knud J. Jensen, Peter Møller, Steffen Loft

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
28 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)380-389
Number of pages10
JournalBasic and Clinical Pharmacology and Toxicology
Issue number4
Early online date21 Oct 2016
Publication statusPublished - Apr 2017


  • Binding Sites
  • Cell Survival/drug effects
  • Coculture Techniques
  • Cytokines/immunology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Endocytosis
  • Endothelial Cells/drug effects
  • Flow Cytometry
  • Human Umbilical Vein Endothelial Cells
  • Integrin alpha5beta1/metabolism
  • Integrin alphaVbeta3/metabolism
  • Integrins/metabolism
  • Lipopolysaccharides/pharmacology
  • Liposomes
  • Macrophages/drug effects
  • Microscopy, Fluorescence
  • Molecular Targeted Therapy
  • Monocytes/drug effects
  • Oligopeptides/chemistry
  • Particle Size
  • Surface Properties


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