Takashi Hasumura

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.

Fluorinated Graphene Oxide; a New Multimodal Material for Biological Applications

Fluorinated graphene oxide (FGO) is reported for the first time as a magnetically responsive drug carrier that can serve both as a magnetic resonance imaging (MRI) and photoacoustic contrast agent, under preclinical settings, and as a type of photothermal therapy. Its hydrophilic nature facilitates biocompatibility. FGO as a broad wavelength absorber, with high charge transfer and strong non-linear scattering is optimal for NIR laser-induced hyperthermia.

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy.

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.

Aptamer-labeled PLGA nanoparticles for targeting cancer cells

Cancer is one of the leading causes of death in most parts of the world and is a very serious cause of concern particularly in developing countries. In this work, we prepared and evaluated the aptamer-labeled paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Apt-PTX-PLGA NPs) which can ameliorate drug bioavailability and enable accurate drug targeting to cancer cells with controlled drug release for cancer therapy. Paclitaxel-loaded PLGA nanoparticles (PTX-PLGA NPs) were formulated by a single-emulsion/solvent evaporation method and were further surface-functionalized with a chemical cross-linker bis(sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. The prepared nanoparticles were characterized by atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Cytotoxicity studies were carried out using normal human mammary epithelial cells (HMEC cells) and human glial cancer cells (GI-1 cells) by methylthiazolyldiphenyl-tetrazolium bromide assay and Alamar blue assay, which confirmed that PTX-PLGA NPs with aptamer conjugation (Apt-PTX-PLGA NPs) were comparatively non-toxic to HMEC cells while toxic to GI-1 cancer cells. Cellular uptake of PTX-PLGA NPs with and without aptamer conjugation was studied using GI-1 cells and monitored by confocal microscopy and phase contrast microscopy. Our studies demonstrated significant internalization and retention of nanoparticles inside the cells, inducing apoptosis. The preferential accumulation of PTX-PLGA NPs within the cancer cells were also confirmed by flow cytometry-based uptake studies. The results indicated that Apt-PTX-PLGA NPs could be a promising targeted therapeutic delivery vehicle for cancer treatment.

Biomimetic smart nanocomposite: in vitro biological evaluation of zein electrospun fluorescent nanofiber encapsulated CdS quantum dots

New hybrid quantum dot (QD)/nanofibers have potential applications in a variety of fields. A novel fluorescent nanocomposite nanofiber material, consisting of CdS and zein has been fabricated through the electrospinning process. A detailed optimization was carried out to fabricate continuous and uniform nanofibers without beads or droplets. The synthesized hybrid nanofibers were characterized by various state-of-the-art techniques such as scanning electron microscopy, transmission electron microscopy (TEM), TEM-energy dispersive spectrometry, atomic force microscopy and confocal fluorescence micrography. The optimization process was carried out to fabricate fibers ranging from 200 to 450 nm in diameter. The electrical conductivity of the zein-CdS hybrid nanofiber substrates was tested. The potential use of the electrospun CdS-encapsulated nanofibrous scaffold as substrates for cell/tissue culture was evaluated with two different cell types, i.e. mesenchymal stem cells and fibroblasts. The results showed that the electrospun fibrous scaffolds could support the attachment and the proliferation of cells. In addition, the cells cultured on the fibrous scaffolds exhibited normal cell shapes and integrated well with surrounding fibers. The obtained results confirmed the potential for the use of the electrospun QD-encapsulated fluorescent nanofiber mats as scaffolds for tissue engineering.

Dissociation of carbon dioxide and creation of carbon particles and films at room temperature

As fluids approach their gas–liquid critical points, the physical properties such as the specific heat and compressibility diverge due to the formation of large molecular clusters. Incident light cannot penetrate near-critical fluids because of the large clusters, a phenomenon known as critical opalescence. In this paper, we irradiate near-critical carbon dioxide (ncCO2), the critical temperature and pressure of which are 31.0°C and 7.38 MPa, with a laser beam of 213, 266, 355 and 532 nm wavelength and show that CO2 is dissociated and particles are produced when the system is set so close to the critical point that critical opalescence occurs in the case of 213 and 266 nm wavelength, whereas no particles are produced when the temperature is made to deviate from the critical value. We also apply a dc electric field to ncCO2 during irradiation with a laser beam of 213 and 266 nm wavelength and find that particles are formed on both anode and cathode. As the intensity of the electric field increases, films are formed on the electrodes. Electron diffraction patterns and energy-dispersive x-ray, Auger electron, x-ray photoelectron and Raman spectroscopic analyses show that the particles and films are composed of amorphous carbon.

Creation of metal-containing carbon onions via self-assembly in metallocene/benzene solution irradiated with an ultraviolet laser

We irradiate sub- and super-critical benzene, in which metallocene such as ferrocene or cobaltocene is dissolved, with a UV laser of 266nm wavelength, and show that benzene and metallocenes are dissociated and iron- and cobalt-containing carbon onions (Fe@C and Co@C) are created. The operational temperature of the present method is much lower than that of conventional ones for the growth of nanomaterials and therefore coagulation among metal-containing carbon onions is avoided. The average diameters of the core iron and cobalt nanoparticles are, respectively, 7.5 and 7.2nm, whereas the thickness of the layers of carbon onions surrounding the core metal particles is 3.2nm in both Fe@C and Co@C cases. The metal-containing carbon onions show superparamagnetic characteristics.

Synthesis of magnetic alloy-filling carbon nanoparticles in super-critical benzene irradiated with an ultraviolet laser

Magnetic nanoparticles are of great importance particularly in the field of biomedicine as well as nanotechnology and nano materials science and technology. Here, we synthesise magnetic alloy-filling carbon nanoparticles (MA@C NPs) via the following two-step procedure; (1) Irradiation of a laser beam of 266 nm wavelength into super-critical benzene, in which both ferrocene and cobaltocene are dissolved, at 290 °C; and (2) annealing of the particles at 600 and 800 °C. We find that the core particles are composed of cobalt (Co), iron (Fe) and oxygen (O) and covered with carbon layers. The structure of the core particles as-synthesised, and annealed at 600 and 800 °C, is, respectively, amorphous, CoFe2O4 and FeCo. We also investigate the viability of L929 cells in the presence of MA@C NPs and find that there is no serious advert effect of the MA@C NPs on the cell viability thanks to the carbon layers covering the core particles. The magnetic properties are well characterised. The saturation and remnant magnetisation and coercivity increase and as a result, the hyperthermic efficiency becomes higher with an increase in the annealing temperature. The further modification of the surface of the present particles with several functional molecules becomes easier due to the carbon layers, which makes the present particles more valuable. It is therefore supposed that the presently synthesised MA@C NPs may well be utilised for nanotechnology-based biomedical engineering; e.g., nano bioimaging, nano hyperthermia and nano surgery.

Low temperature synthesis of carbon fibres and metal-filling carbon nanoparticles with laser irradiation into near-critical benzene

We irradiate near-critical benzene set at 290 °C, in which either an alloy rod composed of mainly iron, chromium, and nickel is placed or copper complex molecules; bis(t-butylacetoacetato)copper(II): Cu(tbaoac)2, are dissolved, with the second (532 nm wavelength), third (355 nm), and fourth (266 nm) harmonics generated from a neodymium doped yttrium/aluminium/garnet (Nd:YAG) laser and show that carbon structures such as fibres, coils, and metal-filling carbon nanoparticles are efficiently produced. The operational temperature is 290 °C, which is much lower than that in the conventional synthetic methods of nano materials, and the laser power density can be as low as 3.9 mW mm−2.

Curcumin nanoparticles- a gateway for multifaceted approach to tackle Alzheimer's disease

Curcumin is a polyphenolic compound which has been used since ages to treat various ailments. Research in the past few decades has demonstrated its potential therapeutic or preventive effects due to its anti-tumor, anti-inflammatory, anti-oxidative, anti-amyloid, anti-arthritic, anti-ischemic to list a few. In our work, we have successfully synthesized curcumin nanoparticles encapsulated in poly lactic-co-glycolic acid (PLGA) which are water soluble. We would like to harness the anti-amyloid, anti-inflammatory and anti-oxidant activities of curcumin to alleviate the amyloid beta level and other associated changes in Alzheimer disease (AD).