Sub-Micrometer Magnetic Nanocomposites: Insights into the Effect of Magnetic Nanoparticles Interactions on the Optimization of SAR and MRI Performance

Abstract

There is increasing interest in the development of new magnetic polymeric carriers for biomedical applications such as trigger-controlled drug release, magnetic hyperthermia (MH) for the treatment of cancer, and as contrast agents in magnetic resonance imaging (MRI). This work describes the synthesis of sub-micrometer and magnetic polymer nanocomposite capsules (MPNCs) by combining in one single platform the biodegradable polymer poly-ϵ-caprolactone (PCL) and different concentrations of ∼8 nm oleic acid (OA)-functionalized magnetite nanoparticles (Fe3O4@OA), employing the oil-in-water emulsion/solvent evaporation method. The MPNCs showed a significant increase in particle size from ∼400 to ∼800 nm as the magnetic loading in the organic-inorganic hybrids increases from 1.0% to 10%. The MPNCs presented high incorporation efficiency of Fe3O4@OA nanoparticles, good colloidal stability, and super-paramagnetic properties. Interestingly, electron microscopy results showed that the Fe3O4@OA nanoparticles were preferentially located at the surface of the capsules. Evaluation of the magnetic properties showed that the saturation magnetization and the blocking temperature of the MPNCs samples increased as a function of the Fe3O4@OA loading. All the MPNCs exhibited heating when subjected to MH, and showed good specific absorption rates. Use of the formulations decreased the longitudinal (T1) and transverse (T2) relaxation times of water protons' nuclei, with excellent transverse relaxivity (r2) values, especially in the case of the formulation with lowest Fe3O4@OA loading. Furthermore, the MPNCs-cell interaction was studied, and MPNCs showed lower cellular toxicity to normal cells compared to cancer cells. These findings help in understanding the relationships between magnetic nanoparticles and polymeric capsules, opening perspectives for their potential clinical uses as simultaneous heating sources and imaging probes in MH and MRI, respectively.