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

Line Hansen, Esben Kjær Unmack Larsen, Erik Holm Nielsen, Frank Iversen, Zhuo Liu, Karen Thomsen, Michael Pedersen, Troels Skrydstrup, Niels Chr. Nielsen, Michael Ploug, Jørgen Kjems

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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 targetmediated 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.
Original languageEnglish
JournalNanoscale
Volume5
Issue number17
Pages (from-to)8192
ISSN2040-3364
DOIs
Publication statusPublished - 2013
Externally publishedYes

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