Magnetically Induced Brownian Motion of Iron Oxide Nanocages in Alternating Magnetic Fields and Their Application for Efficient siRNA Delivery.

Hyperthermia of superparamagnetic nanoparticles driven by Néel relaxation in an alternating magnetic field (AMF) has been studied in biomedical areas; however, Brownian motion, induced by another magnetic relaxation mechanism, has not been explored extensively despite its potential in intracellular mechanoresponsive applications. We investigated whether superparamagnetic cage-shaped iron oxide nanoparticles (IO-nanocages), previously demonstrated to carry payloads inside their cavities for drug delivery, can generate Brownian motion by tuning the nanoparticle size at 335 kHz AMF frequency. The motivation of this work is to examine the magnetically driven Brownian motion for the delivery of nanoparticles allowing escape from endosomes before digestion in lysosomes and efficient delivery of siRNA cargoes to the cytoplasm. Superconducting quantum interference device (SQUID) measurements reveal the nanocage size dependence of Brownian relaxation, and a magnetic Brownian motion of 20 nm IO-nanocages improved the efficiency of siRNA delivery while endosomal membranes were observed to be compromised to release IO-nanocages in AMFs during the delivery process.

Application of functionalized nanoparticle for mass spectrometry.

We synthesized functionalized nanoparticles (NPs) by in mixing aqueous solutions of 3d transition metal (iron, or manganese) chlorides (MCl2 x nH2O) and (3-aminopropyl)triethoxysilane, and in this unique method, monodispersed NPs were obtained in a single step. The prepared NPs examined by X-ray diffraction, transmission electron microscope, Fourier transform infrared spectroscopy and zeta potential measurement. The synthesized NPs surround by amorphous SiO2 and possess amino and hydroxyl groups on NPs surface. The number-average diameter of the NPs was determined to be about 3 and 5 nm. The NPs worked as an ionization assisting reagent in mass spectrometry (MS) by means of what is called nanoparticle assisted laser desorption/ionization (nano-PALDI) MS has begun to be used to analyze low molecular compound. In this paper, we introduced analysis of the food product and pesticide as environmental pollutant by using nano-PALDI MS.

Preparation and magnetic properties of multiferroic CuMnO2 nanoparticles.

CuMnO2 nanoparticles with diameters of 64 nm were synthesized by a novel wet chemical method. An optimized two-step annealing method was developed through the analysis of thermogravimetric differential thermal analysis (TG-DTA) measurements in order to obtain single-phase CuMnO2. A sharp exothermic peak was observed in the DTA curve at approximately 500 K where structural changes of the copper oxides and manganese oxides in the precursor are expected to occur. It is believed that Cu+ ions were oxidized to Cu2+ ions and that Mn2+ ions were oxidized to Mn3+ ions in the Cu-Mn-O system. Deoxidization reactions were also found at approximately 1200 K. The optimized annealing temperature for the first step was determined to be 623 K in air. The optimized annealing temperature for the second step was 1173 K in an Ar atmosphere. Magnetization measurements suggested an antiferromagnetic spin ordering at approximately 50 K. It was expected that Mn3+ spin interactions induced magnetic phase transition affected by definite temperature.

Characterization of magnetic and dielectric properties of Bi(1-x)Gd(x)FeO3 nanoparticles by local structure analyses.

Bi(1-x)Gd(x)FeO3 (0 < or = x < or = 1.0) nanoparticles were synthesized by a wet chemical method. The annealing temperatures were controlled to obtain single-phase Bi(1-x)Gd(x)FeO3 nanoparticles. The crystal diameters decreased as the number of doped Gd ions increased. The crystal structure changed, as the number of Gd ions increased, from rhombohedral to orthorhombic perovskite, at x = 0.2. The behavior of the magnetization curves observed at various values of x (x = 0.05, 0.1, 0.15) of the rhombohedral structure suggested that the canted antiferromagnetism and remanent magnetization (M(r)) drastically increased, compared with those at x = 0 (BiFeO3). It is suggested that the spin-canting angle of the Fe ions increased with the increase in the number of Gd ions. The dielectric properties at x = 0.1 showed that the dielectric loss (tan delta) was improved, compared with that at x = 0 (BiFeO3), by approximately 90%, while the real part of the dielectric constant epsilon' was reduced by approximately 15%. The reason is that the doping impurities restrained the reduction in the leakage current. It was found, from the X-ray absorption fine structure (XAFS) spectra, that Gd ions were doped accurately and that the symmetry of the B site was improved. The Mössbauer analysis suggested the existence of magnetic cycloid spiral ordering.

Oligonucleotide analysis by nanoparticle-assisted laser desorption/ionization mass spectrometry.

We analyzed oligonucleotides by nanoparticle-assisted laser desorption/ionization (nano-PALDI) mass spectrometry (MS). To this end, we prepared several kinds of nanoparticles (Cr-, Fe-, Mn-, Co-based) and optimized the nano-PALDI MS method to analyze the oligonucleotides. Iron oxide nanoparticles with diammonium hydrogen citrate were found to serve as an effective ionization-assisting reagent in MS. The mass spectra showed both [M - H](-) and [M + xMe(2+)- H](-) (Me: transition metal) peaks. The number of metal-adducted ion signals depended on the length of the oligonucleotide. This phenomenon was only observed using bivalent metal core nanoparticles, not with any other valency metal core nanoparticles. Our pilot study demonstrated that iron oxide nanoparticles could easily ionize samples such as chemical drugs and peptides as well as oligonucleotides without the aid of an oligonucleotide-specific chemical matrix (e.g., 3-hydroxypicolinic acid) used in conventional MS methods. These results suggested that iron-based nanoparticles may serve as the assisting material of ionization for genes and other biomolecules.

Nanotrap and mass analysis of aromatic molecules by phenyl group-modified nanoparticle.

To functionalize the surface of nanoparticles with phenyl groups for subsequent cross-linking with aromatic molecules by mutual interactions, we prepared functional nanoparticles (d = 3 nm) by silanization with phenyl-triethoxysilane. The nanoparticles had Fe(2)O(3) cores conjugated to phenyl groups; this was confirmed by Fourier transform infrared (FT-IR) spectroscopy and absorption spectrophotometry. The typical C-H and C-C peaks and the absorption at 240 nm, which corresponds to aromatic rings, were detected in the spectroscopic results for the phenyl group-modified nanoparticles. The nanoparticles could ionize aromatic (colchicine, reserpine, and bradykinin peptide) and nonaromatic (L-α-phosphatidylethanolamine,dioleoyl, and polyethylene glycol) molecules by nanoparticle-assisted laser desorption/ionization mass spectrometry. The nanoparticles worked as a selective trap and an ionization-assisting reagent in mass spectrometry for the aromatic molecular targets.

PEGylation of Co-Zn Ferrite Nanoparticles for Theranostics.

Multi-element ferrite nanoparticles (NPs) were synthesized as heat agents for use in magnetic hyperthermia treatments, specifically, Co0.8Zn0.2Fe2O4 NPs coating with polyethylene glycol. The crystal structures of these particles were examined by X-ray diffraction. Particle diameters were controlled to be approximately 10 nm by controlling the annealing temperature and time. The modification of polyethylene glycol (PEG) on the particles was confirmed by mass spectrometry and Fourier-transform infrared spectrometry. The heat dissipation characteristics of the particles were investigated by measuring AC magnetic susceptibility and temperature increase in AC magnetic fields. A peak in the imaginary part of AC magnetic susceptibility χ″ appeared, depending on the frequency. The value of χ″ was found to contribute to the effective heat dissipation according to the Neel relaxation system. The temperature increase of the particles was measured in AC magnetic fields of 64-146 Oe, with an observed temperature increase of ~10 K. Finally, to test the applications of these particles in theranostics, in vitro experiments using human breast cancer cells were conducted.

Functionalized magnetic nanoparticles as an in vivo delivery system.

We developed extremely small functionalized magnetic nanoparticles (MNPs) for use as an in vivo delivery system for pharmaceuticals and biomolecules. We functionalized the MNPs (d = 3 nm) by silanization of amino groups on the particles with (3-aminopropyl)triethoxysilane for subsequent cross-linking with pharmaceuticals and biomolecules. The MNPs were successfully introduced into living cells without any further modification, such as the use of cationic residues, to enhance endocytic internalization. The particles could be incorporated into the subcutaneous tissue of a mouse's ear through the skin of the ear and could be localized by application of an external magnetic field.We also developed a cell-specific delivery system that makes use of MNPs (d = 3 nm) conjugated with folic acid and a coumarin fluorophore for recognition by folate receptors on the cell surface. The modified MNPs were internalized by human pharyngeal cancer cells (KB cells) after an incubation time that was short compared with the time required for internalization of MNPs without folic acid. Cellular recognition of MNPs may lead to the development of other cell-specific delivery systems.These functionalized MNPs are expected to be useful as a new drug delivery tool.

Magnetic nanoparticle-based mass spectrometry for the detection of biomolecules in cultured cells.

We prepared functionalized magnetic nanoparticles (d = 3.5 nm) to serve as a laser desorption/ionization material for mass spectrometry. The obtained nanoparticles consisteds of a macaulayite core conjugated with hydroxyl and amino groups, and showed superparamagnetism at room temperature. The nanoparticles by themselves could ionize the sample peptide, drug and proteins (approx. 5000 Da) without causing background peaks. In the detection of biomolecules by mass spectrometry, the analytes are generally extracted from biological samples, and undergo futher purification and desaltation. However, these processing steps cause analyte loss. In the present study, we tried to detecting biomolecules in cultured cells without extraction or desaltation, but by using nanoparticles and a permanent magnet. The nanoparticles were introduced into living cells cultured on indium tin oxide-coated glass slides and accumulated on the surface of the cultured cells using an external magnetic field. The direct mass spectrometry of the cultured cells showed that we successfuly profiled the phospholipids of the cells. Our new nanoparticle-assisted laser desorption/ionization mass spectrometry technique is a quick and convenient way to profile biomolecules in cultured cells.

Manganese oxide nanoparticle-assisted laser desorption/ionization mass spectrometry for medical applications.

We prepared and characterized manganese oxide magnetic nanoparticles (d =5.6 nm) and developed nanoparticle-assited laser desorption/ionization (nano-PALDI) mass spectrometry. The nanoparticles had MnO2 and Mn2O3 cores conjugated with hydroxyl and amino groups, and showed paramagnetism at room temperature. The nanoparticles worked as an ionization assisting reagent in mass spectroscopy. The mass spectra showed no background in the low m/z. The nanoparticles could ionize samples of peptide, drug and proteins (approx. 5000 Da) without using matrix, i.e., 2,5-dihydroxybenzoic acid (DHB), 4-hydroxy-α-cinnamic acid (CHCA) and liquid matrix, as conventional ionization assisting reagents. Post source decay spectra by nano-PALDI mass spectrometry will yield information of the chemical structure of analytes.

Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution.

Today, two-dimensional mass spectrometry analysis of biological tissues by means of a technique called mass imaging, mass spectrometry imaging (MSI), or imaging mass spectrometry (IMS) has found application in investigating the distribution of moleculesMSI with matrix-assisted laser desorption/ionization (MALDI) and secondary ion MS (SIMS). However, the size of the matrix crystal and the migration of analytes can decrease the spatial resolution in MALDI, and SIMS can only ionize compounds with relatively low molecular weights. To overcome these problems, we developed a nanoparticle-assisted laser desorption/ionization (nano-PALDI)-based MSI. We used nano-PALDI MSI to visualize lipids and peptides at a resolution of 15 microm in mammalian tissues.

Functionalized nano-magnetic particles for an in vivo delivery system.

Nanotechnologies to allow the nondisruptive introduction of carriers in vivo have wide potential for therapeutic delivery system. We have prepared functional nano-magnetic particles (d = 3 nm) by silanization with (3-aminopropyl) triethoxysilane. For the purpose of functionalizing the surface of the nanoparticles with amino groups for subsequent cross-linking with pharmaceuticals and biomolecules. The extremely small particles were successfully introduced into living cells without any further modification to enhance endocytic internalization, such as the use of a cationic help. The cells containing the internalized particles continued to thrive, indicating that the particles have no inhibition effect for mitosis. In addition, the particles could be incorporated into the subcutaneous tissue of mouse's ear from ear skin and were able to be localized upon application of an external magnetic field. The functionalized nano-magnetic particles are expected to be useful as a new delivery tool.

Silver Oxide Based Nanoparticle Assisted Laser Desorption/Ionization Mass Spectrometry for the Detection of Low Molecular Weight Compounds.

A specific property of silver oxide-based nanoparticles permits the ionization of an analyte, giving rise to various applications of a smart analytical methodology. The nanoparticles (d=6.7 nm) contained an Ag2O core. The detection of several model componds (a nucleobase and two hair growth promoters) via the use of silver oxide nanoparticles is described. Adducts were produced between the target molecules and the two silver stable isotopes (Ag(107) and Ag(109)), resulting in the formation of specific signals as well as a protonated signal. Thus, it was possible to easily determine whether the given signals were correlated with the target molecule or not.