A Swiss army knife for the treatment of bone cancers: a new multifunctional platform based upon SPIONS@copper-doped bioactive glass core-shell nanoparticles

Abstract

In this study, magnetic γ-Fe2O3@SiO2-CaO-CuO mesoporous copper-doped bioactive glass core-shell nanoparticles (MCSNs) were synthesised by iron salts co-precipitation, and by a modified Stöber sol-gel method, using a cationic surfactant CTAB as templating agent. All samples were characterized with a large set of techniques including X-Ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), Transmission Electron Microscopy (TEM), nitrogen gas sorption, Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Magic Angle Spinning-Nuclear Magnetic Resonance (MAS-NMR). Magnetic characterisations were carried out by AC magnetometry and NMR relaxometry to establish a proof of material capacity to produce heat under an Alternative Magnetic Field (AMF), predict its magnetic behaviour and determine whether it can act as contrast agent in magnetic resonance imaging. The specific adsorption rate (SAR) values were obtained in a large AMF conditions range. Relaxometry measurements confirm the possibility of using those materials as negative (T2-weighted) contrast agent in magnetic resonance imaging (MRI). Finally, in vitro bioactivity was evaluated after immersion in Simulated Body Fluid (SBF) at 37°C. All sample showed hydroxyapatite crystal formation delay kinetic for copper doped sample. The cytotoxic evaluation indicated a dose-dependent effect. At 0.25 mg/mL, none of the tested samples presented signs of cytotoxicity after 7 days. Antibacterial assessments were also performed with both methicillin resistant and sensitive Staphylococcus aureus. The highly copper doped material shows a significant antibacterial effect. This study represents the first step in the development of a multifunctional synthetic biocompatible nanomaterial combining bone regeneration and antibacterial effect, under possible monitoring by MRI and a potential cancer treatment by magnetic hyperthermia.