Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells. / Hansen, Line; Larsen, Esben Kjær Unmack; Nielsen, Erik Holm; Iversen, Frank Horsbøl; Liu, Zhuo; Thomsen, Karen Sand; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr; Ploug, Michael; Kjems, Jørgen.
In: Nanoscale, Vol. 5, No. 17, 07.09.2013, p. 8192-201.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells
AU - Hansen, Line
AU - Larsen, Esben Kjær Unmack
AU - Nielsen, Erik Holm
AU - Iversen, Frank Horsbøl
AU - Liu, Zhuo
AU - Thomsen, Karen Sand
AU - Pedersen, Michael
AU - Skrydstrup, Troels
AU - Nielsen, Niels Chr
AU - Ploug, Michael
AU - Kjems, Jørgen
PY - 2013/9/7
Y1 - 2013/9/7
N2 - Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.
AB - Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.
KW - Amino Acid Sequence
KW - Click Chemistry
KW - Ferric Compounds
KW - Fluorescent Dyes
KW - HEK293 Cells
KW - Humans
KW - Magnetite Nanoparticles
KW - Microscopy, Confocal
KW - Peptides
KW - Polyethylene Glycols
KW - Protein Binding
KW - Receptors, Urokinase Plasminogen Activator
U2 - 10.1039/c3nr32922d
DO - 10.1039/c3nr32922d
M3 - Journal article
C2 - 23835641
VL - 5
SP - 8192
EP - 8201
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 17
ER -
ID: 107124749