title: A multimodal magnetic resonance imaging nanoplatform for cancer theranostics.
abstract: We describe an innovative multimodal system, which combines magnetic targeting of therapeutic agents with both magnetic resonance and fluorescence imaging into one system. This new magnetic nanoplatform consists of superparamagnetic γFe(2)O(3) nanoparticles, used clinically as an MRI contrast agent, conjugated to therapeutic molecules of the hydroxylmethylene bisphosphonate family (HMBPs): alendronate with an amine function as the terminal group. In vitro tests with breast cancer cells show that the γFe(2)O(3)@alendronate hybrid nanomaterial reduces cell viability and acts as a drug delivery system. We also investigated the anti-tumoural properties in vivo in nude mice xenografted with MDA-MB-231 tumours. We show that the presence of both γFe(2)O(3)@alendronate and a magnetic field significantly reduced the development of tumours. The amine functionalities can be used as precursor groups for the covalent coupling of peptides or monoclonal antibodies for specific biological targeting. The feasibility of this process was demonstrated by coupling rhodamine B, a fluorescence marker, to the γFe(2)O(3)@alendronate nanohybrid. The system showed fluorescent properties and high affinity for cells. Flow cytometry and fluorescence microscopy were used to study the kinetics of γFe(2)O(3)@alendronate uptake by cells. The magnetic and fluorescent nanoparticles are potential candidates for smart drug-delivery systems. Also, the superparamagnetic behaviour of such nanoparticles may be exploited as MRI contrast agents to improve therapeutic diagnostics.
authors.affiliation: Laboratory CSPBAT, UMR 7244 CNRS, University Paris 13, 93017 Bobigny, France.
authors.forename: Farah
authors.initials: F
authors.lastname: Benyettou
authors.forename: Yoann
authors.initials: Y
authors.lastname: Lalatonne
authors.forename: Imène
authors.initials: I
authors.lastname: Chebbi
authors.forename: Mélanie
authors.initials: M
authors.lastname: Di Benedetto
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Serfaty
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.forename: Laurence
authors.initials: L
authors.lastname: Motte
mesh_terms: D019386:Alendronate / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D019386:Alendronate