Synthesis, modeling and optimization of iron oxide nanoparticles for magnetic fluid hyperthermia.

摘要

Magnetic fluid hyperthermia (MFH) is the controlled heating of tissue to febrile temperature ranges to promote cellular damage/death as an alternative cancer therapy. The heat generated in MFH is the result of magnetic nanoparticles responding to an ac-magnetic field. The advantage of this treatment is the possibility of a targeted and triggered treatment which can reduce damage to healthy tissue. Another great potential of the technique is the possibility of combined diagnostics and treatment within a single platform by combing MFH with Magnetic Resonance Imaging (MRI). The fundamental challenges lie in the formulation of the magnetic nanoparticles, specifically increasing and predicting heating rates. While many groups have used nanoparticles made from known toxic materials, this work focuses solely on iron oxide because of its tolerability in vivo.;Heating rates were increased by improving the material properties of the nanoparticles. Theory indicates that heat generation with superparamagnetic particles is intimately linked to particle, size, shape and surface modification. A synthesis method not commonly used for biomedical applications was used to produce monodisperse, highly crystalline, phase pure magnetite nanoparticles with size control from 2--11 nm. However, the as-synthesized particles were not dispersible in aqueous solutions, therefore a coating method was developed to phase transfer the particles. Cytotoxicity studies were performed to optimize the coating method to ensure that the final formulation was not toxic to cells when measured up to concentrations of 1.2 mg Fe/mL.;This work, for the first time, includes the affects of polydispersity and interparticle interactions on heating rates. Models indicate that 10-11 nm particles will result in the highest heat within biologically-compatible limitations. Calorimetry results indicate that heating rates up to 450 W/g Fe3O4 are achievable and that polydispersity decreases the nanoparticle's ability to generate heat. Results indicated that interparticle interactions can arise because of concentration, agglomeration or due to concentration within cells.;Initial MRI relaxivity studies indicate that these nanoparticles show great promise as contrast enhancers, however the maximum working concentration prior to saturation of MR images ∼ 10 mug Fe/mL may be too small to generate sufficient heating rates for MFH.