Abstract
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.
Highlights
Breast cancer is the most common malignancy in women throughout the world, accounting for more than 25% of all new cancer diagnoses in 2012, and despite significant improvements in treatment, for 522,000 deaths [1]
Among the nanotechnology tools investigated for biomedical applications are the intrinsic magnetic properties exhibited by iron oxide nanoparticles (MNP), which may be used for magnetic resonance imaging in diagnosis and for magnetic hyperthermia in cancer thermotherapy [3,4], as well as for controlled drug delivery [5,6]
Various quantities of N6L pseudopeptide were covalently immobilized onto magnetic nanoparticles (MNP) and the zeta potential values at the different functionalization steps were monitored
Summary
Breast cancer is the most common malignancy in women throughout the world, accounting for more than 25% of all new cancer diagnoses in 2012, and despite significant improvements in treatment, for 522,000 deaths [1]. These facts clearly indicate the need to improve existing breast cancer treatments and to develop new therapeutic strategies. Nanomedicine, the application of nanotechnology to medicine, is a promising approach for specific cancer cell targeting, diagnosis, and treatment [2]. Novel multi-functionalization strategies of MNP with cytotoxic drugs and targeting agents, enabling drug release mainly within tumor cells by the development of intracellular medium-triggered linkers seem to be promising strategies for cancer therapy
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