Banalata Sahoo

Thermal and pH responsive polymer-tethered multifunctional magnetic nanoparticles for targeted delivery of anticancer drug.

Targeted and efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, we report a temperature and pH dual responsive core-shell nanoparticles comprising smart polymer shell coated on magnetic nanoparticles as an anticancer drug carrier and cancer cell-specific targeting agent. Magnetite nanoparticles (MNPs), prepared by a simple coprecipitation method, was surface modified by introducing amine groups using 3-aminopropyltriethoxysilane. Dual-responsive poly(N-isopropylacrylamide)-block-poly(acrylic acid) copolymer, synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, was then attached to the amine-functionalized MNPs via EDC/NHS method. Further, to accomplish cancer-specific targeting properties, folic acid was tethered to the surface of the nanoparticles. Thereafter, rhodamine B isothiocyanate was conjugated to endow fluorescent property to the MNPs required for cellular imaging applications. The nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), zeta potential, vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS) measurements, and FTIR, UV-vis spectral analysis. Doxorubicin (DOX), an anticancer drug used for the present study, was loaded into the nanoparticles and its release behavior was subsequently studied. Result showed a sustained release of DOX preferentially at the desired lysosomal pH and temperature condition. The biological activity of the DOX-loaded MNPs was studied by MTT assay, fluorescence microscopy, and apoptosis. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into cancer cells (HeLa cells) compared to normal fibroblast cells (L929 cells). The in vitro apoptosis study revealed that the DOX-loaded nanoparticles caused significant death to the HeLa cells. These nanoparticles were capable of target specific release of the loaded drug in response to pH and temperature and hence may serve as a potential drug carrier for in vivo applications.

Biocompatible mesoporous silica-coated superparamagnetic manganese ferrite nanoparticles for targeted drug delivery and MR imaging applications

Multifunctional mesoporous silica-coated superparamagnetic manganese ferrite (MnFe2O4) nanoparticles (M-MSN) were synthesized and evaluated for targeted drug delivery and magnetic resonance imaging (MRI) applications. MnFe2O4 nanoparticles were prepared by solvothermal route and were silica-coated by surface silylation using sol-gel reactions. Subsequently, silylation was done using (3-aminopropyl)triethoxysilane in presence of a surfactant (CTAB), followed by selective etching of the surfactant molecules that resulted in amine-functionalized superparamagnetic nanoparticles (NH2-MSN). Further modification of the surface of the NH2-MSN with targeting (folate) or fluorescent (RITC) molecules resulted in M-MSN. The formation of the M-MSN was proved by several characterization techniques viz. XRD, XPS, HRTEM, FESEM, VSM, BET surface area measurement, FTIR, and UV-Vis spectroscopy. The M-MSN were loaded with anticancer drug Doxorubicin and the efficacy of the DOX loaded M-MSN was evaluated through in vitro cytotoxicity, fluorescence microscopy, and apoptosis studies. The in vivo biocompatibility of the M-MSN was demonstrated in a mice-model system. Moreover, the M-MSN also acted as superior MRI contrast agent owing to a high magnetization value as well as superparamagnetic behavior at room temperature. These folate-conjugated nanoparticles (FA-MSN) exhibited stronger T2-weighted MRI contrast towards HeLa cells as compared to the nanoparticles without folate conjugation, justifying their potential importance in MRI based diagnosis of cancer. Such M-MSN with a magnetic core required for MRI imaging, a porous shell for carrying drug molecules, a targeting moeity for cancer cell specificity and a fluorescent molecule for imaging, all integrated into a single system, may potentially serve as an excellent material in biomedical applications.

Fabrication of magnetic mesoporous manganese ferrite nanocomposites as efficient catalyst for degradation of dye pollutants

In this study, mesoporous silica encapsulated with magnetic MnFe2O4 nanoparticles is synthesized by a solvothermal method. The synthetic route is feasible and widely applicable. The obtained products have been characterized by an X-ray powder diffraction (XRD) pattern, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM) and nitrogen adsorption–desorption isotherm measurements. The synthesized magnetic mesoporous MnFe2O4 nanoparticles are monodispersed with a mean diameter of 200 nm, and have an obvious mesoporous silica shell of ∼20 nm. The surface area of magnetic mesoporous MnFe2O4 nanocomposites is 423 m2 g−1. The nanoparticles are superparamagnetic in nature at room temperature and can be separated by an external magnetic field. This magnetic mesoporous material is used as a catalyst for the degradation of methyl orange dye. The merits of the effect under different conditions like pH, temperature, light and sonolysis have been evaluated by investigating the degradation of azo dye. The mesoporous MnFe2O4 nanocomposites have effective adsorption of dyes inside the porous network followed by degradation with the central magnetite core and regeneration of the catalyst with the help of a simple magnet for successive uses.

Facile preparation of uniform barium titanate (BaTiO3) multipods with high permittivity: impedance and temperature dependent dielectric behavior

Perovskite barium titanate (BaTiO3) multipods were prepared via high temperature solid state reaction. The crystal structure and morphology of BaTiO3 particles were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), and scanning probe microscopy (SPM). The XRD analysis of the crystal structure revealed that a single-phase compound was formed having tetragonal crystal structure. Calorimetric study (DSC) over room to high temperature was used to find the energy involved in different steps of synthesis especially during the initiation and the termination process for the formation of BaTiO3. These multipods have high average aspect ratio (∼10, where average diameter ∼300 nm and average length ∼3 μm) as seen from FESEM. UV-Vis spectroscopy reveals that the prepared material is UV active. The bulk and surface chemical composition of these BaTiO3 particles as investigated by Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) spectra reveals that in the prepared BaTiO3, the titanium ions exist in two different oxidation states, namely Ti3+ and Ti4+. The BaTiO3 multipod exhibits high permittivity with relatively low dielectric loss. From impedance analysis of the material, the dual resistivity characteristics, one for grain and the other for grain-boundary can be distinguished. An equivalent circuit has been proposed through analysis of the complex impedance plot (Nyquist plot) for BaTiO3 multipods. This material has perfect capacitative nature as seen from the Bode plot, and can be used for charge storage devices and other electronic applications. From temperature dependent dielectric analysis, the Curie temperature of BaTiO3 multipods is found to be ∼85 °C.

Facile preparation of multifunctional hollow silica nanoparticles and their cancer specific targeting effect

Efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, we have established a facile and unique chemical strategy for fabrication of highly biocompatible and water-dispersible multifunctional hollow silica nanoparticles (HSNPs). These mesoporous silica nanoparticles, having ring-like morphology, were fabricated by the sol-gel method followed by selective etching of the inner inorganic core. Further, to accomplish cancer-specific targeting properties, folic acid was tethered to the surface of HSNPs through amide bond formation using the EDC/NHS coupling method. Thereafter, rhodamine B isothiocyanate (RITC) was conjugated to the HSNPs to endow the fluorescent property to the nanoparticles required for biological imaging applications. The successful formation of multifunctional HSNPs was confirmed by XRD, FTIR, zeta potential, TEM, FESEM, and BET surface area measurements. The average particle size of HSNPs was found to be 50 nm to 70 nm from TEM analysis, which is the desired size-range for drug-delivery vehicles. These HSNPs showed good mesoporous behavior and were found to be an excellent candidate for loading and releasing the anticancer drug doxorubicin (DOX). The bioactivity of the HSNPs was verified by biological assay including cell cytotoxicity by MTT assay, intracellular uptake by fluorescence microscopy, cell cycle analysis by fluorescence-activated cell sorting (FACS), and apoptosis study. Besides, the effect of salt concentration on the drug release performance was evaluated. An in vitro biological study revealed that these DOX-loaded folate-targeted HSNPs achieved excellent efficacy for simultaneously targeting and destroying cancer cells.

Characterization and lectin microarray of an immunomodulatory heteroglucan from Pleurotus ostreatus mycelia

Glucans isolated from various mushroom and mycelia sources are interestingly being studied nowadays as a potent therapeutic agent. The present work was focused on the isolation, characterization and immunomodulatory study of a novel water soluble glucan from the pure mycelia of Pleurotus ostreatus. The extracted glucan was found to have a high molecular weight of ∼2.7 × 10(6)Da and mainly comprised of glucose, mannose and fucose in a ratio of 3:2:1 with both β and α linkages. Presence of terminal or interior glucose, mannose and fucose residues was also revealed using a high throughput miniaturized platform of lectin microarray. The heteroglucan folded into a triple helical conformation and exhibited enhanced immune cell activation and anti-tumor potential in tumor bearing mice model. Thus, potential biological functions incorporated in these glucan molecules acts in accord with its structural property and exploration of such structure-function relationship will unveil its diverse mechanism of action.

Development of polyurethane–titania nanocomposites as dielectric and piezoelectric material

Flexible polyurethane (PU)–titania nanocomposites of different compositions are prepared by a melt-mixing technique. Two different sequences of mixing method are adapted to prepare two different sets of composites. All these composites show composition-dependent dielectric properties, and composites with tunable dielectric properties can be obtained through judicial adjustment of composition. The morphology of these composites has been investigated by field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), and scanning probe microscopy (SPM). Dielectric properties at low frequency regions are found to depend on morphology. These composites show excellent piezoelectric behaviour, where the dielectric constant and conductivity of these flexible composites change appreciably with changes in applied stress. The dielectric breakdown strength of these composite is also measured. To understand the thermal stability of these composites, thermogravimetric analysis has been applied and it was found that a composite containing 12.49 vol% titania shows higher thermal stability, beyond which, stability decreases due to the photocatalytic effect of titania.

Amine-functionalized magnetic nanoparticles as robust support for immobilization of Lipase

AbstractPreparation of magnetic nanoparticles with controlled size and shape along with modulation of their surface properties via introduction of functional groups holds great prospect in the field of nanotechnology. Superparamagnetic, aqueous dispersible iron oxide nanoparticles (Fe3O4) with amine-functionalized surface were prepared through solvothermal method, using poly(ethylene imine) (PEI), ethanolamine (EA), and 2,2 ′-(ethylenedioxy)bis(ethylamine) (EDBE) as amine precursors. These aminated nanoparticles were used as support for the immobilization of lipase, an important industrial enzyme. Lipase was immobilized via glutaraldehyde coupling agent. These functionalized nanoparticles were characterized by XRD, FTIR, TEM, FESEM and VSM analysis. The maximum activity was obtained for the lipase immobilized on EDBE modified Fe3O4 nanoparticles. The lipase immobilized on EDBE-Fe3O4 depicted 83.9% relative activity with respect to the same amount of free lipase. Moreover, lipase immobilized on EDBE-Fe3O4 nanoparticles demonstrated good thermal and storage stability, and easy reusability. The kinetic parameters of lipase immobilized on EDBE-Fe3O4 were compared with those of free lipase and the apparent Michaelis-Menten constant of immobilized lipase was found to be nearly same as that of free lipase. Graphical AbstractMonodispersed, amine-functionalized magnetic nanoparticles have been obtained through one-pot method. These nanoparticles behaved as excellent support for lipase immobilization with improved stability and resusability.

Nanoparticle and polysaccharide conjugate: A potential candidate vaccine to improve immunological stimuli

Active polysaccharides isolated from various fungal sources have been implicated to stimulate immune response against various pathogens as well as self anomalies such as cancer. Therefore, the nuanced approach presented in our work was to blend polysaccharides derived from Pleurotus ostreatus with biocompatible ferrite nanoparticles and thereafter investigate the enhanced immune functionality of the polysaccharide-nanoparticle composite. A Schiff base reductive amination reaction occurred between the aldehyde group of the polysaccharide and the amine group of the nanoparticles in the presence of a strong reducing agent such as sodium cyanoborohydride to form a stable amide bond between the two conjugating molecules. The multifaceted conjugate was characterized by physiochemical techniques such as electron microscopy, FTIR, VSM and DLS measurements. This particulate form of the polysaccharide showed a marked escalation in the production of free radicals such as reactive oxygen and nitrogen species in murine macrophages as compared to the soluble form. Animal based experiments demonstrated a reduction in tumor volume and augmentation in the proliferation of splenocytes in particulate or conjugated polysaccharide treated mice. Furthermore, molecular signaling studies showed a high upregulation in p-p38 and p-MEK molecules in particulate polysaccharide treated RAW264.7 cells suggesting a cellular downstream mechanistic regulation behind the immunostimulative response.

Heteroglucan-dendrimer glycoconjugate: a modulated construct with augmented immune responses and signaling phenomena

BACKGROUND Newer strategies for augmenting immune responses of pharmacologically active glucans may serve to improve the medicinal potential of these biomolecules. With this aim, the present work was focused on generating targeted high molecular size glucan particles with magnified immune response activity. METHODS Heteroglucans were conjugated with PAMAM dendrimers using a Schiff base reductive amination reaction to generate a polytethered molecule with multiple glucan motifs. The modulated construct was characterized by FTIR, TEM, (1)H NMR and dynamic light scattering (DLS) methods. Effects of conjugated glucans were examined in RAW 264.7 macrophage cells as well as in S-180 murine tumor models. RESULTS Dendrimer-conjugated glucans were found to exhibit a two-fold increase in immune stimulation in comparison to unconjugated glucans. This may be corroborated by the predominant enhancement in immunological functions such as nitric oxide production, ROS generation and immune directed tumor inhibition in murine models. Immune cell surface markers (CD4, CD8, CD19, MHC-II) and cytokine levels were also found to be highly up-regulated in the splenocytes of mice subjected to particulate glucan administration. Our study also demonstrated that conjugated glucan treatment to RAW 264.7 cells strongly enhanced the phosphorylation of two downstream signalling molecules of the mitogen activated protein kinase (MAPKs) family: p38 and MEK1/2 relative to single glucans thereby relating molecular mechanisms with enhanced immune stimulation. CONCLUSIONS AND GENERAL SIGNIFICANCE The results obtained thus support that particulate format of soluble heteroglucan will thereby improve its functionality and identify leads in therapeutic competence.