Effect of Surface Modification via Silica Shells on Magnetic Properties of Iron Oxide Nanoparticles

Silica shell formation on nanoparticles via reverse microemulsion is one of the most promising ways to obtain biocompatible surface states. Furthermore, the silica layer is easily functionalized with versatile functional groups, which provides researchers with a universal design platform. However, for magnetic nanoparticles (MNPs) composed of magnetite or tertiary ferrites, commonly used for biological applications including hyperthermia and modulation of cell signaling, it was reported that the silica layer degrades the magnetic properties. The interaction between the silica shell and ferrite core diminishes the magnetic anisotropy, and thus the specific loss power (SLP, heating efficientcy in W/g_[Metal]) decreases. High SLP is necessary for MNPs to work as effective mediators of magnetothermal modulation of cell signaling. Additionally, further functionalization of the silica layer tends to increase the shell thickness, further decreasing the magnetic anisotropy and lowering the SLP values.<br/><br/>To suppress the degradation of MNP properties, creating thin (one or few layers) silica shells offers a promising approach, and several groups have conducted parameter studies to create thinner shells on MNPs used as magnetic resonance imaging (MRI) contrast agents. However, the size of MNPs for modulation of cell signaling or hyperthermia is larger (20-25nm) than those used as MRI contrast agents (10-15 nm), which means the number of particles differs by an order of magnitude for the same mass of material. Since the number ratio between nanoparticles and reverse micelles is critical during microemulsion synthesis, the conditions to make thin silica shells must be reconsidered.<br/><br/>We have developed a robust protocol for forming and functionalizing thin silica shells on 20-25 nm MNPs, a size range that shows the highest SLPs among metal-oxide nanoparticles under mild magnetic field conditions (H×<i>f </i>&lt; 5×10⁹ A/m･s). Additionally, the relationship between SLP and silica shell thickness has been investigated. Through the protocol development, the significance of the crystal phase of magnetic cores to obtain uniform shells was uncovered. The influence of further biologically-motivated functionalization with amine groups or thiol groups has also been evaluated.