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 γFe₂O₃ 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 γFe₂O₃@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 γFe₂O₃@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 γFe₂O₃@alendronate nanohybrid. The system showed fluorescent properties and high affinity for cells. Flow cytometry and fluorescence microscopy were used to study the kinetics of γFe₂O₃@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.