Magnetic Nanoparticles for Theranostics. (Invited)

Abstract

Magnetic nanoparticles have attracted attention for biomedical applications. One of the author reported original preparation method of magnetic nanoparticles (MNPs), and the way of functionalization by amino-silane coupling procedure [1]. We tried to introduce these functional particles into the living cells, and these particles were localized by the external magnetic field. Then cancer cell selective NPs were further developed by conjugating with folic acid [2]. We have also suggested that these magnetic nanoparticles can be utilized in biomedical applications, such as hyperthermia treatment [3] or MRI agent [4], for producing functional magnetic nanoparticles. These magnetic nanoparticles are expected as agents for future theranostics, namely, performing therapy and diagnostics simultaneously [5]. Effective heat dissipation for magnetic hyperthermia treatment in AC field depends on the magnetic relaxation parameters. Several kinds of ferrite NPs were prepared and AC magnetic measurements were performed in order to improve heating effect of MNPs for hyperthermia treatment. The relationship between imaginary part of AC magnetic susceptibility χ” and increase in temperature in the AC field was estimated. The particle size and composition of the samples were varied and examined. Fig.1 shows temperature dependence of imaginary part of AC magnetic susceptibility χ” for various particle size of Co 0.3 Fe 2.7 O 4 nanoparticles in a 1 Oe, 100 Hz field. The temperature rise of this sample upon an alternative field was measured, and it was found that the temperature increased by about 20 K under AC frequency of 15 kHz and field of 210 Oe. From the result of the temperature increase rate, heat dissipation was evaluated quantitatively according to Neel relaxation theory. An AC field was found to cause an increase in temperature, with the 7.5 nm particles exhibiting the highest temperature increase as expected. Therefore, finally in vitro experiments to study the hyperthermia effects of Co 0.3 Fe 2.7 O 4 particles on cancerous cells were carried out. Drastic effect of magnetic hyperthermia was observed. (Fig.2) Imaging methods are one of the effective tools for diagnostics. Specifically, magnetic resonance imaging (MRI) and mass spectrometric imaging (MSI) [6], and MNPs can be used to improve these imaging methods. Currently, main components of γ-Fe 2 O 3 and Fe 3 O 4 have been used for MRI contrast agents to emphasize the relaxation time of $T_{2}$ in the clinical scene. We synthesized Co-ferrite nanoparticles surrounded by amorphous SiO 2 , and the relationship between these MR relaxivity and physical properties was investigated by spin echo sequence. The $T_{2}$ relaxation curves of CoFe 2 O 4 .nSiO 2 (n=1,3,6 and removed Si) and other sample γ-Fe 2 O 3 , Fe 3 O 4 and agarose for comparison were measured. These samples also had larger $R_{2}$ compared with conventional materials such as γ-Fe 2 O 3 , Fe 3 O 4 and background. The parameters of T2 and R2 varied depending on only Si composition even same metal compositions, same particle size. It is considered that distance between nanoparticle and proton would be increased as the thickness of SiO 2 shell increased. Furthermore, dispersibility of nanoparticles was improved under the influence of negative charge carried SiO 2 layer. Magnetic particle imaging (MPI) and CT (X-ray tomography) imaging using our particles are in progress. Our metal oxide nanoparticles and their hybrid materials with organic compounds are anticipated to find use in the area of multifunctional nanomedicine such as magnetic hyperthermia and MRI contrast agents, called “Theranostics”