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Functionalization of Iron Oxide Magnetic Nanoparticles with the Multivalent Pseudopeptide N6l for Breast Tumor Targeting

Maha Sader, Pierre Couleaud, Gilles Carpentier, Maud-Emmanuelle Gilles, Noureddine Bousserrhine, Alexandre Livet, Ilaria Cascone, Damien Destouches, Aitziber L Cortajarena and José Courty

Functionalized iron oxide magnetic nanoparticles (MNP) are an innovative tool for cancer detection and treatment. In this study, a cell-surface nucleolin antagonist, N6L, was used as targeting ligand for MNP. This N6L, which exhibits antitumor activities, specifically targets bind tumor cells by binding to cell-surface nucleolin and glycosaminoglycans. N6L was covalently conjugated to dimercaptosuccinic acid coated magnetic nanoparticles (MNP-N6L). Using immunoprecipitation, gene invalidation and enzymatic degradation of glycosaminoglycans, we showed that MNP-N6L targets human breast cancer MDA-MB 231 cells through interaction with nucleolin and sulfated glycosaminoglycans. In vivo biodistribution studies were carried out in MDA-MB 231 tumor-bearing mice, using iron detection assay by spectrometric analysis and Prussian blue staining. Whereas both non-functionalized and functionalized nanoparticles were found in liver and spleen, only MNP-N6L was found in the tumor. Our findings indicate that MNP-N6L is a promising targeting system for theranostic applications in cancer detection and treatment.