Hisao Morimoto

Curcumin Loaded-PLGA Nanoparticles Conjugated with Tet-1 Peptide for Potential Use in Alzheimer's Disease

Alzheimers disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimers disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimers disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimers disease proving it to be a potential therapeutic tool against this dreaded disease.

Aptamer conjugated magnetic nanoparticles as nanosurgeons

Magnetic nanoparticles have shown promise in the fields of targeted drug delivery, hyperthermia and magnetic resonance imaging (MRI) in cancer therapy. The ability of magnetic nanoparticles to undergo surface modification and the effect of external magnetic field in the dynamics of their movement make them an excellent nanoplatform for cancer destruction. Surgical removal of cancerous or unwanted cells selectively from the interior of an organ or tissue without any collateral damage is a serious problem due to the highly infiltrative nature of cancer. To address this problem in surgery, we have developed a nanosurgeon for the selective removal of target cells using aptamer conjugated magnetic nanoparticles controlled by an externally applied three-dimensional rotational magnetic field. With the help of the nanosurgeon, we were able to perform surgical actions on target cells in in vitro studies. LDH and intracellular calcium release assay confirmed the death of cancer cells due to the action of the nanosurgeon which in turn nullifies the possibility of proliferation by the removed cells. The nanosurgeon will be a useful tool in the medical field for selective surgery and cell manipulation studies. Additionally, this system could be upgraded for the selective removal of complex cancers from diverse tissues by incorporating various target specific ligands on magnetic nanoparticles.

Activity of an enzyme immobilized on superparamagnetic particles in a rotational magnetic field

We immobilize alpha-amylase extracted from Bacillus Iicheniformis on the surfaces of superparamagnetic particles and investigate the effect of a rotational magnetic field on the enzymes activity. We find that the activity of the enzyme molecules immobilized on superparamagnetic particles increases in the rotational magnetic field and reaches maximum at a certain frequency. We clarify the effect of the cluster structures formed by the superparamagnetic particles on the activity. Enzyme reactions are enhanced even in a tiny volume of solution using the present method, which is very important for the development of efficient micro reactors and micro total analysis systems (mu-TAS).

Activity of Lipase and Chitinase Immobilized on Superparamagnetic Particles in a Rotational Magnetic Field

We immobilize hydrolases such as lipase and chitinase on superparamagnetic particles, which are subjected to a rotational magnetic field, and measure the activities of the enzymes. We find that the activities of lipase and chitinase increase in the rotational magnetic field compared to those in the absence of a magnetic field and reach maximum at certain frequencies. The present methodology may well be utilized for the design and development of efficient micro reactors and micro total analysis systems (μ-TASs).

Ordered complex structures formed by paramagnetic particles via self-assembly under an ac/dc combined magnetic field.

We apply ac and dc magnetic fields simultaneously in orthogonal directions to each other to a solution, in which paramagnetic microparticles are dispersed, and show that complex secondary structures composed of oscillating chain clusters, that is, long linear clusters interconnected by T-, L-, and criss-cross-junctions, are self-assembled. Disklike clusters are formed at some junctions and the number of disklike clusters increases as the frequency of the ac magnetic field increases. We finally show that the angle between long linear clusters can be altered by changing the ratio of the intensities of the ac and dc magnetic fields.

Ring-chain structural transitions in a ferromagnetic particles system induced by a dc magnetic field

We carry out statistical analysis of cluster structures formed by ferromagnetic particles in a dc magnetic field based on a flexible chain model. In the absence of a magnetic field, ferromagnetic particles tend to form ring structures. When a dc magnetic field is applied, the rings are broken into chains if the intensity of the field is sufficiently high since the dipole moment of each particle is aligned in the field direction. We analyze the conditions under which ring-chain structural transitions occur and clarify the dependence of the probabilities of the creation of ring and chain structures on control parameters such as the strength of the dipole-dipole interactive energy between particles, the intensity of the magnetic field and the cluster size.

DYNAMIC ANALYSIS OF A FERROMAGNETIC COLLOIDAL SYSTEM

We studied cluster structures formed in two- and three-dimensional magnetic fluid systems numerically. We developed a Brownian dynamics calculation method in which both the translational and rotational motions of ferromagnetic particles were taken into account. The cluster formations are analysed from the point of view of second order phase transition and the dependence of the cluster size on the temperature and magnetic field is investigated. The fractal dimensions were, respectively, 1.3 and 1.6 for the two- and three-dimensional systems in the absence of a magnetic field. On the other hand, the fractal dimension was very close to 1.0 for both two- and three-dimensional systems when the system was subjected to a magnetic field. The cluster-cluster aggregations are also investigated and the validity of the dynamic scaling law is examined. It has been found that the fractal dimensions obtained by the dynamic analysis coincide with those obtained by the analysis of the cluster structures. The critical exponents were 0.7 and 0.8 in the absence of a magnetic field and in a magnetic field, respectively, in the case of the two-dimensional system, and 1.2 and 0.8 in the case of the three-dimensional system for λ=12 where λ is the ratio of magnetic dipole energy to thermal energy.

Particle ordering at the initial stage of colloidal crystallization: implication for non-classical dynamic behavior

Abstract The particle ordering dynamics of polystyrene colloids were studied using low-angle laser light scattering and Brownian dynamics (BD) simulation. The polystyrene particles were prepared in the highly deionized water and crystalline states were realized after shear melting due to vigorous circulation of fluids. The radius of gyration of crystalline clusters was evaluated by the laser light scattering and showed the rapid increase of cluster size similar to percolation dynamics with increasing crystalline fraction. The following dynamics were confirmed by BD simulation. The ordered domains were formed under the repulsive potential of latex particles and extended to all over the sample within a relatively short time. The domains were connected as in percolation transitions at a critical threshold. This means that the critical clusters are not compact as in the final crystal but form a rather loose structure in the nucleation stage of colloidal crystallization. The consistent results between experiments and simulation indicate a new ordering dynamics from metastable liquid, which is quite different from the standard nucleation minimizing the free energy of critical nucleus.

Capture of nonmagnetic particles and living cells using a microelectromagnetic system

We develop a microelectromagnetic system to trap nonmagnetic materials such as micropolystyrene particles and yeast cells in particular areas. We fabricate gold films, the width of the central narrow part is 22 μm, and flow an electric current through the films. We then apply an external uniform dc magnetic field to weaken the local magnetic field at the narrow part so that a nonuniform magnetic field is produced. We demonstrate that the particles, which are dispersed in magnetic fluid, are successfully trapped at the narrow part of the film. We evaluate the driving force acting on a microparticle in the nonuniform magnetic field and carry out a Stokesian dynamics simulation of the motion of the particles. We show that yeast cells are also trapped at the narrow part of the film. Finally, we fabricate multichannel microelectromagnets so that yeast cells are trapped at multiple points in the microelectromagnetic system. The present system may be applied to cell transfection on a cell microarray and, therefo...

GROWTH OF COLLOIDAL CRYSTALS UNDER MICROGRAVITY

The growth dynamics of colloidal crystallization was evaluated under sedimentation free conditions using sounding rocket and Brownian Dynamics (BD) simulation. The Braggs reflections of colloidal crystals were measured during microgravity flight and average sizes of crystallites were obtained by the Sherrers method. Results showed a power-law relationship between size and time, L ∝ tα where L is the size of crystallites and t is time. The obtained α s were 0.33 ± 0.03 in microgravity and 0.25 ± 0.02 in normal gravity, respectively. Browninan Dynamics (BD) simulation showed the time evolution of ordered domains that consisted of connected structures of crystalline clusters. The power law relationship n ∝ t0.5 in post-nucleation period was confirmed between the number of particles (n) in clusters and time. The calculated power was related to α using the fractal dimension of crystalline clusters and α = 0.31 was obtained. The value was matched well with that of the microgravity experiment.