1 Ploug Group, BRIC Research Groups, BRIC, Københavns Universitet2 Interdisciplinary Nanoscience Center - INANO-MBG, iNANO-huset3 Interdisciplinær Nanoscience Forskerskole4 Forest & Landscape Denmark, Faculty of Life Sciences, Københavns Universitet5 Molekylærbiologisk Institut6 Aalborg University7 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet8 Institut for Kemi, Aarhus Universitet9 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet10 Interdisciplinary Nanoscience Center11 Forest & Landscape Denmark, Faculty of Life Sciences, Københavns Universitet12 Aalborg University13 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet14 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet15 Ploug Group, BRIC Research Groups, BRIC, Københavns Universitet
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.