Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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Yn: Basic & clinical pharmacology & toxicology, Cyfrol 120, Rhif 4, 04.2017, t. 380-389.
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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TY - JOUR
T1 - Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells
AU - Kermanizadeh, Ali
AU - Villadsen, Klaus
AU - Østrem, Ragnhild G
AU - Jensen, Knud J
AU - Møller, Peter
AU - Loft, Steffen
N1 - © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
KW - Binding Sites
KW - Cell Survival/drug effects
KW - Coculture Techniques
KW - Cytokines/immunology
KW - Dose-Response Relationship, Drug
KW - Drug Delivery Systems
KW - Endocytosis
KW - Endothelial Cells/drug effects
KW - Flow Cytometry
KW - Human Umbilical Vein Endothelial Cells
KW - Integrin alpha5beta1/metabolism
KW - Integrin alphaVbeta3/metabolism
KW - Integrins/metabolism
KW - Lipopolysaccharides/pharmacology
KW - Liposomes
KW - Macrophages/drug effects
KW - Microscopy, Fluorescence
KW - Molecular Targeted Therapy
KW - Monocytes/drug effects
KW - Oligopeptides/chemistry
KW - Particle Size
KW - Surface Properties
U2 - 10.1111/bcpt.12692
DO - 10.1111/bcpt.12692
M3 - Article
C2 - 27767251
VL - 120
SP - 380
EP - 389
JO - Basic & clinical pharmacology & toxicology
JF - Basic & clinical pharmacology & toxicology
SN - 1742-7835
IS - 4
ER -