Immobilization of cholesterol oxidase in a conducting copolymer of thiophene-3-yl acetic acid cholesteryl ester with pyrrole

Cholesterol oxidase has been immobilized in conducting copolymers of thiophene-3-yl acetic acid cholesteryl ester with pyrrole (CM/PPy) and polypyrrole (PPy) via electropolymerization. p-Toluene sulphonic acid was used as the supporting electrolyte. Kinetic parameters (V-max and K-m) and operational stability of enzyme electrodes were investigated. Surface morphology of the films was examined by scanning electron microscope

Polysulfone/Clay Nanocomposites by in situ Photoinduced Crosslinking Polymerization

Cataloged from PDF version of article.PSU/MMT nanocomposites are prepared by dispersing MMT nanolayers in a PSU matrix via in situ photoinduced crosslinking polymerization. Intercalated methacrylate-functionalized MMT and polysulfone dimethacrylate macromonomer are synthesized independently by esterification. In situ photoinduced crosslinking of the intercalated monomer and the PSU macromonomer in the silicate layers leads to nanocomposites that are formed by individually dispersing inorganic silica nanolayers in the polymer matrix. The morphology of the nanocomposites is investigated by XRD and TEM, which suggests the random dispersion of silicate layers in the PSU matrix. TGA results confirm that the thermal stability and char yield of PSU/MMT nanocomposites increases with the increase of clay loading

Immunostimulatory activity of polysaccharide-poly(I:C) nanoparticles

Cataloged from PDF version of article.Immunostimulatory properties of mushroom derived polysaccharides (PS) as stand-alone agents were tested. Next. PS were nanocomplexed with polyI:C (pIC) to yield stable nanoparticles around 200 nm in size evidenced by atomic force microscopy and dynamic light scattering analyses. PSs were selectively engaged by cells expressing TLR2 and initiated NF kappa B dependent signaling cascade leading to a Th1-biased cytokine/chemokine secretion in addition to bactericidal nitric oxide (NO) production from macrophages. Moreover, cells treated with nanoparticles led to synergistic IL6, production and upregulation of TNF alpha, MIP3 alpha, IFN gamma and IP10 transcript expression. In mice, PS-Ovalbumin-pIC formulation surpassed anti-OVA IgG responses when compared to either PS-OVA or pIC-OVA mediated immunity. Our results revealed that signal transduction initiated both by TLR2 and TLR3 via co-delivery of pIC by PS in nanoparticle depot delivery system is an effective immunization strategy. The present work implicate that the PS and nucleic acid based nanoparticle approach along with protein antigens can be harnessed to prevent infectious diseases. (C) 2011 Elsevier Ltd. All rights reserve

Heparin Mimetic Peptide Nanofibers Promote Angiogenesis

Cataloged from PDF version of article.New blood vessel formation (angiogenesis) is one of the most important processes required for functional tissue formation. Induction of angiogenesis is usually triggered by growth factors released by cells. Glycosaminoglycans (e.g., heparan sulphates) in the extracellular matrix aid in proper functioning of these growth factors. Therefore, exogeneous heparin or growth factors were required for promoting angiogenesis in previous regenerative medicine studies. Here we report for the first time induction of angiogenesis by a synthetic nanofibrous peptide scaffold without the addition of any exogenous growth factors or heparin. We designed and synthesized a self-assembling peptide amphiphile molecule that is functionalized with biologically active groups to mimic heparin. Like heparin, this molecule has the ability to interact with growth factors and effectively enhance their bioactivity. The nanofibers formed by these molecules were shown to form a 3D network mimicking the structural proteins in the extracellular matrix. Because of heparin mimicking capabilities of the peptide nanofibers, angiogenesis was induced without the addition of exogenous growth factors in vitro. Bioactive interactions between the nanofibers and the growth factors enabled robust vascularization in vivo as well. Heparin mimetic peptide nanofibers presented here provide new opportunities for angiogenesis and tissue regeneration by avoiding the use of heparin and exogenous growth factors. The synthetic peptide nanofiber scaffolds enriched with proper chemical functional groups shown in this study can be used to induce various desired physiological responses for tissue regeneration. © 2011 American Chemical Society

Cetuximab-Ag₂S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells

Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoprophyrin IX (PpIX) based photodynamic therapy (PDT) is already approved in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. Combination of effective ALA-PDT with chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy is proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet endowed excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which are high, medium and low EGFR expressers. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 were determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkage was also effective for PDT, but required longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based Chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and an excellent potential for synergistic multistage tumour targeting therapy

Polystyrene/clay nanocomposites by atom transfer radical nitroxide coupling chemistry

An efficient protocol, atom transfer radical nitroxide coupling chemistry, for the preparation of polymer/clay nanocomposites via grafting-onto strategy with well-defined polymer, which were synthesized via atom transfer radical polymerization, has been described. The radical coupling, taking place between the clay layers, not only leads to attached polymer chains but also to successful nanocomposite formation with highly exfoliated morphology. Copyright © 2012 Wiley Periodicals, Inc

Polarization study of single color centers in aluminum nitride

Color centers in wide-bandgap semiconductors are a promising class of solid-state quantum light source, many of which operate at room temperature. We examine a family of color centers in aluminum nitride, which emits close to 620 nm. We present a technique to rapidly map an ensemble of these single photon emitters, identifying all emitters, not just those with absorption dipole parallel to the laser polarization. We demonstrate a fast technique to determine their absorption polarization orientation in the c-plane, finding they are uniformly distributed in orientation, in contrast to many other emitters in crystalline materials

Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis

In this subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285), we evaluated efficacy and safety of the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with carfilzomib-dexamethasone (Isa-Kd) versus Kd in older (≥70 years of age, n = 86) and younger (<70 years, n = 216) patients with relapsed multiple myeloma (MM). Patients received Isa 10 mg/kg intravenously weekly for 4 weeks, then every 2 weeks in the Isa-Kd arm, and approved schedule of carfilzomib (twice weekly) and dexamethasone in both study arms. Primary endpoint was progression-free survival (PFS); key secondary efficacy endpoints included rates of overall response (ORR), very good partial response or better (≥VGPR), minimal residual disease negativity (MRD–), and complete response (CR). Addition of Isa to Kd resulted in improved PFS in elderly patients (hazard ratio, 0.36 [95% CI, 0.18–0.75]) consistent with the significant PFS improvement observed in the overall IKEMA population. Treatment with Isa-Kd improved depth of response versus Kd, with higher rates of ≥VGPR (73.1% vs. 55.9%), MRD– (23.1% vs. 11.8%), and CR (38.5% vs. 23.5%). Although the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was higher in Isa-Kd, the incidence of serious TEAEs was similar between arms. Fewer elderly patients definitively discontinued treatment due to TEAEs in Isa-Kd than Kd: 11.8% versus 23.5%. In conclusion, Isa-Kd provides a consistent benefit versus Kd in elderly patients, with a manageable safety profile, and represents a new treatment option for patients with relapsed MM, independent of age

Repetition rate tuning of an ultrafast ytterbium doped fiber laser for terahertz time-domain spectroscopy

Repetition rate tuning enables the fast acquisition of THz pulse profiles [1]. By using this method we demonstrate a compact and broadband terahertz time domain spectroscopy system (THz TDS) driven by ytterbium doped fiber laser source. The importance of this method is realized in that Yb:doped fiber lasers can be amplified to sub-millijoule pulse strengths more easily than other types of fiber lasers [2]. Hence, it has the potential to be used in excite-THz probe experiments. Furthermore, the repetition rate-tuning adds flexibility in the excite-probe techniques. These attributes as well as THz generation and detection are investigated with the laser that was developed. © 2013 IEEE