Yoshitaka Kitamoto

Nanomedicine for cancer: lipid-based nanostructures for drug delivery and monitoring.

Recent advances in nanotechnology, materials science, and biotechnology have led to innovations in the field of nanomedicine. Improvements in the diagnosis and treatment of cancer are urgently needed, and it may now be possible to achieve marked improvements in both of these areas using nanomedicine. Lipid-coated nanoparticles containing diagnostic or therapeutic agents have been developed and studied for biomedical applications and provide a nanomedicine strategy with great potential. Lipid nanoparticles have cationic headgroups on their surfaces that bind anionic nucleic acids and contain hydrophobic drugs at the lipid membrane and hydrophilic drugs inside the hollow space in the interior. Moreover, researchers can design nanoparticles to work in combination with external stimuli such as magnetic field, light, and ionizing radiation, which adds further utility in biomedical applications. In this Account, we review several examples of lipid-based nanoparticles and describe their potential for cancer treatment and diagnosis. (1) The development of a lipid-based nanoparticle that included a promoter-enhancer and transcriptional activator greatly improved gene therapy. (2) The addition of a radiosensitive promoter to lipid nanoparticles was sufficient to confer radioisotope-activated expression of the genes delivered by the nanoparticles. (3) We successfully tailored lipid nanoparticle composition to increase gene transduction in scirrhous gastric cancer cells. (4) When lipophilic photosensitizing molecules were incorporated into lipid nanoparticles, those particles showed an increased photodynamic cytotoxic effect on the target cancer. (5) Coating an Fe(3)O(4) nanocrystal with lipids proved to be an efficient strategy for magnetically guided gene-silencing in tumor tissues. (6) An Fe(16)N(2)/lipid nanocomposite displayed effective magnetism and gene delivery in cancer cells. (7) Lipid-coated magnetic hollow capsules carried aqueous anticancer drugs and delivered them in response to a magnetic field. (8) Fluorescent lipid-coated and antibody-conjugated magnetic nanoparticles detected cancer-associated antigen in a microfluidic channel. We believe that the continuing development of lipid-based nanomedicine will lead to the sensitive minimally invasive treatment of cancer. Moreover, the fusion of different scientific fields is accelerating these developments, and we expect these interdisciplinary efforts to have considerable ripple effects on various fields of research.

Faraday effect enhancement in Co–ferrite layer incorporated into one-dimensional photonic crystal working as a Fabry–Pérot resonator

We fabricated a one-dimensional magnetophotonic crystal (MPC), in which a magnetic layer of Co–ferrite (∼40 nm in thickness) is sandwiched by a couple of dielectric multilayer reflectors with (SiO2/TiO2)×7 structure. The Co–ferrite layer was synthesized by ferrite plating from aqueous solution at 90 °C. The MPC is so designed to enhance magneto-optical Faraday rotation θF at the Fabry–Perot resonance wavelength λ of the multilayer structure. θF was observed to increase by factor of ∼5.4, but at λ=∼620 nm which is deviated from the target resonance (λ=740 nm) and at very weak transmissivity. This may be because the Co–ferrite layer is rough in surface and smaller in thickness than the target thickness at which Fabry–Perot resonance is designed to occur.

Co ferrite films with excellent perpendicular magnetic anisotropy and high coercivity deposited at low temperature

The present article describes CoxFe3−xO4 films, which were fabricated at 90 °C by the ferrite-plating method and have the excellent perpendicular magnetic anisotropy and the perpendicular coercivity Hc⊥ above 2 kOe. The films were composed of Co ferrite and Fe3O4 grains. The highest Hc⊥ reached 3 kOe at the composition of Co0.43Fe2.57O4 and the saturation magnetization Ms was 500–550 emu/cc. Hc⊥ was over 2 kOe even for a film thickness of 35 nm without any underlayers. ΔM⊥ evaluation that is measured in the perpendicular direction to the film plane showed that the interactions in the films supported the magnetized state, stabilizing the direct current remanent state. The Mossbauer analyses revealed that the Co0.43Fe2.57O4 films have excellent perpendicular magnetic anisotropy and the magnetization direction inclined from the perpendicular axis due to the demagnetization field. This achievement will open the way to develop the high-density perpendicular recording media even when plastic disks and sheets ar...

Magnetotransport study of temperature dependent magnetic anisotropy in a (Ga,Mn)As epilayer

The anisotropic magnetotransport properties of a (Ga,Mn)As epilayer and the magnetization switching are studied as a function of temperature. The magnetization switching field shows asymmetry for crystallographically equivalent [110] and [110] directions at 4 K, and the asymmetry is more significant at 40 K. The magnetization switching features clearly show that cubic magnetocrystalline anisotropy along 〈100〉, which is biased by a small uniaxial anisotropy along the [110] easy axis, is dominant at 4 K. On the other hand, the [110] uniaxial anisotropy competes with the cubic anisotropy and dominates the magnetization switching at 40 K. Accordingly, the magnetization reversal in the (Ga,Mn)As epilayer occurs via 90° and 180° domain-wall displacement at 4 and 40 K, respectively. A mechanism of the change in the magnetic anisotropy is discussed within a theoretical description of the hole band structure.

A magnetically guided anti-cancer drug delivery system using porous FePt capsules☆

Magnetic carriers with efficient loading, delivery, and release of drugs are required for magnetically guided drug delivery system (DDS) as the potential cancer therapy. The present article describes the fabrication of porous FePt capsules approximately 340 nm in diameter with large pores of 20 nm in an ultrathin shell of 10 nm and demonstrates their application to a magnetically guided DDS in vitro. An aqueous anti-cancer drug is easily introduced in the hollow space of the capsules without external stimuli and released to cancer cells on cue through the magnetic shell composed of an ordered-alloy FePt network structure, which exhibits superparamagnetic features at approximately body temperature. The drug-loaded magnetic capsules coated with a lipid membrane are efficiently guided to the cancer cells within 15 min using a NdFeB magnet (0.2 T), and more than 70% of the cancer cells are destroyed.

Crystallization of amorphous CoFeB ferromagnetic layers in CoFeB/MgO/CoFeB magnetic tunnel junctions

We demonstrate that the crystallization of ferromagnetic CoFeB layers originates at the interface with a MgO layer in CoFeB/MgO/CoFeB magnetic tunnel junctions by annealing using cross-sectional transmission electron microscopy and electron diffraction. The CoFeB layers, which are amorphous in the as-deposited state, crystallize with a (001) out-of-plane texture by annealing at 360 °C. Crystal grains of 15–20 nm in the CoFeB layers are observed at the interface with the MgO layer, but not at the interface with a Ta or Ru layer. Much smaller crystal grains with random crystal orientations are formed in a region away from the MgO interface in the CoFeB layers. The depth profiles obtained by X-ray photoelectron spectroscopy show that boron diffuses from the crystallized region at the interface into the MgO layer and the rest of the region in the CoFeB layers during crystallization, indicating that crystal grains have much lower B contents than the original composition.

Cation order and magnetic properties of double perovskite Sr2FeMoO6

A double perovskite type compound Sr2FeMoO6 was synthesized by a solid-state reaction. The order parameter (x) of Fe and Pt ions on the B sites increased from 68% to 82% and the spontaneous magnetization at 5 K increased from 2.1 to 3.0 μB per formula unit by lowering the calcination temperature from 1100 to 500 °C. The dependence of the spontaneous magnetization on x was discussed using two models considering the local magnetic interactions between ions on the B sites. 57Fe Mossbauer analysis suggested the existence of tiny areas of SrFeO3−δ in Sr2FeMoO6.

Ferromagnetic FePt-Nanoparticles/Polycation Hybrid Capsules Designed for a Magnetically Guided Drug Delivery System

The present Article describes the synthesis of ferromagnetic capsules approximately 330 nm in diameter with a nanometer-thick shell to apply to magnetic carriers in a magnetically guided drug delivery system. The magnetic shell of 5 nm in thickness is a nanohybrid, composed of ordered alloy FePt nanoparticles of approximately 3-4 nm in size and a polymer layer of a cationic polyelectrolyte, poly(diaryldimethylammonium chloride) (PDDA). The magnetic capsules have an excellent capacity for carrying medical drugs and genes. Surface-modified silica particles with PDDA were used as a template for the capsules. FePt nanoparticles were deposited on the PDDA-modified silica particles through a polyol method followed by dissolving the silica particles with a NaOH solution, resulting in the formation of the magnetic capsules as the final product. A three-dimensional hollow structure is maintained by the nanohybrid shell. The FePt-nanoparticles/PDDA nanohybrid shell also exhibits a ferromagnetic feature at room temperature because the FePt nanoparticles of an ordered-alloy phase are formed with the aid of PDDA despite the small size (3-4 nm).

Mixed magnetic phases in (Ga,Mn)As epilayers.

Two different ferromagnetic-paramagnetic transitions are detected in (Ga,Mn)As/GaAs(001) epilayers from ac susceptibility measurements: transition at a higher temperature results from (Ga,Mn)As cluster phases with [110] uniaxial anisotropy and that at a lower temperature is associated with a ferromagnetic (Ga,Mn)As matrix with 100 cubic anisotropy. A change in the magnetic easy axis from [100] to [110] with increasing temperature can be explained by the reduced contribution of 100 cubic anisotropy to the magnetic properties above the transition temperature of the (Ga,Mn)As matrix.

Connected nanoparticle catalysts possessing a porous, hollow capsule structure as carbon-free electrocatalysts for oxygen reduction in polymer electrolyte fuel cells

We employ connected nanoparticle catalysts with a porous, hollow capsule structure as carbon-free electrocatalysts for the cathode in polymer electrolyte fuel cells (PEFCs) or proton exchange membrane fuel cells (PEMFCs). The catalysts consist of fused ordered alloy platinum–iron (Pt–Fe) nanoparticles. This unique beaded network structure enables surprisingly high activity for the oxygen reduction reaction, 9 times that of the state-of-the-art commercial catalyst. Because the connected nanoparticle catalysts are formed without sacrificing the high surface area of the nanoparticles and can conduct electrons, the catalysts show good performance in an actual PEMFC without a carbon support. Moreover, the elimination of carbon intrinsically solves the problem of carbon corrosion. Thus, the connected nanoparticle catalysts with a unique structure are a significant advancement over conventional electrode catalysts and will lead to an ultimate solution for PEMFC cathodes.