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 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.
| Original language | English |
|---|---|
| Journal | Nanoscale |
| Volume | 5 |
| Issue number | 17 |
| Pages (from-to) | 8192-201 |
| Number of pages | 10 |
| ISSN | 2040-3364 |
| DOIs | |
| Publication status | Published - 7 Sept 2013 |
Keywords
- Amino Acid Sequence
- Click Chemistry
- Ferric Compounds
- Fluorescent Dyes
- HEK293 Cells
- Humans
- Magnetite Nanoparticles
- Microscopy, Confocal
- Peptides
- Polyethylene Glycols
- Protein Binding
- Receptors, Urokinase Plasminogen Activator
