Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

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

SN - 2040-3364

VL - 5

SP - 8192

EP - 8201

JO - Nanoscale

JF - Nanoscale

IS - 17

ER -