2,796 research outputs found

    Self-assembly of peptide-based nanostructures: Synthesis and biological activity

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    Peptide-based nanostructures have received much attention in the field of drug targeting. In fact, peptides have many advantages such as simplicity of the structure, biocompatibility, and chemical diversity. Moreover, some peptides, which are called cell-penetrating peptides, can cross cellular membranes and carry small molecules, small interfering RNA, or viruses inside live cells. These molecules are often covalently or noncovalently linked to cargoes, thus forming amphiphilic conjugates that can self-assemble. Supramolecular nanostructures formed from peptides are used in nanomedicine as a carrier to protect a drug and to target cancer cells. This review explores aliphatic-chain–conjugated peptides and drug-conjugated peptides that can self-assemble. Special emphasis is placed on the synthesis procedure, nanostructure formation, and biological activity

    Enhanced internalization of lipid nanocapsules in human glioblastoma cells: Influence of the concentration of surface-functionalizing NFL peptide

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    Glioblastoma multiforme (GBM) patients have median survival of 14 months after current treatments. Therefore, more efficacious therapies are necessary. Lipid nanocapsules (LNC) functionalized with NFL.TBS-40.63 peptide (NFL) showed enhanced internalization in mouse GBM cells. The aim of the study was to evaluate the effect of the surface-functionalizing FAM-NFL (fluoNFL) concentrations on LNC uptake in U87MG human GBM cells. A ferrocifen-type anticancer molecule (FcTriOH) was encapsulated in the nanocarriers and their in vitro efficacy on U87MG cells was evaluated. Finally, in vivo antitumor effect of the formulations were evaluated in ectopic U87MG tumor model in mice

    Surface-functionalization with NFL peptide of Lipid NanoCapsules LNC: preferential entry into human glioblastoma cells

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    Glioblastoma (GBM) is one of the most fatal brain cancers with median survival of only 14.6 months. Hence, more efficacious therapies are necessary. Ferrocifen (FcTriOH) is an organometallic antitumor compound, selectively active on cancer cells [1]. However, this metallocomplexe is highly insoluble in water, requiring a formulation stage before being in vivo administered. Lipid nanocapsules (LNC), prepared via a solvent free process of emulsion phase inversion, could be a suitable vehicle for FcTriOH [2]. Moreover, NFL peptide is able to enter massively into glioblastoma cells, and poorly in healthy neurons and astrocytes (NHA) [3]. Indeed, the aim of the study was to evaluate the effect of the surface-functionalizing NFL concentrations on LNC uptake in U87MG human GBM cells. Moreover, FcTriOH was encapsulated in LNC and their in vitro efficacy on U87MG cells was evaluated. Finally, in vivo antitumor effect was evaluated in ectopic and orthotopic murine U87MG tumor models. Fluorescent LNC (F1), LNC with 0.86% w/w and LNC with 2.58% w/w surface-adsorbed NFL (F2 and F3 respectively) were prepared and characterized. FACS analysis revealed that cellular uptake of F3 into U87MG cells was 31.5 and 1.6-folds higher after 6 h compared to F1 and F2 respectively. Moreover, uptake of F3 was significantly higher in the GBM cells compared to NHA, whereas F1 was internalized preferentially in NHA. Uptake of F3 in U87MG cells was energy dependent. Macropinocytosis was possibly the major uptake pathway, followed by clathrin-dependent endocytosis. Then, FcTriOH loaded LNCs have been successfully prepared with a drug loading of 2.4 % and an encapsulation efficacy of 99 %. MTS assay on U87MG cells revealed an IC50 of 0.46 µM for F3-FcTriOH (free FcTriOH: IC50 = 1.31 µM). Preliminary in vivo experiments on subcutaneous U87MG tumor bearing nude mice showed significantly reduced relative tumor volume after two intravenous injections of F1-FcTriOH and F3-FcTriOH compared to saline. Moreover, intracranial administration of F3/F3-FcTriOH in orthotopic U87MG tumor bearing mice revealed 2 to 3-folds higher apparent diffusion coefficients (ADC) near the injection site in diffusion tensor imaging, compared to F1/F1-FcTriOH. Although dose adjustment will be necessary to avoid toxic effects, the results are promising as therapy induced increased ADC values could indicate possible cell necrosis/lysis.   References [1] Laine A.L. et al. (2014), Nanomedicine, 10, pp.1667-1677. [2] Heurtault B. et al. (2003), EJPS, 8, pp. 55-61. [3] Balzeau J. et al. (2013), Biomaterials, 34, pp.3381-3389

    Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

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    The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table

    A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

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    We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 fb1{\rm fb}^{-1} recorded at the Υ(4S)\Upsilon(4S) resonance and 3.9 fb1{\rm fb}^{-1} off-resonance. One of the neutral B mesons, which are produced in pairs at the Υ(4S)\Upsilon(4S), is fully reconstructed in the CP decay modes J/ψKS0J/\psi K^0_S, ψ(2S)KS0\psi(2S) K^0_S, χc1KS0\chi_{c1} K^0_S, J/ψK0J/\psi K^{*0} (K0KS0π0K^{*0}\to K^0_S\pi^0) and J/ψKL0J/\psi K^0_L, or in flavor-eigenstate modes involving D()π/ρ/a1D^{(*)}\pi/\rho/a_1 and J/ψK0J/\psi K^{*0} (K0K+πK^{*0}\to K^+\pi^-). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds Δmd=0.516±0.016(stat)±0.010(syst)ps1\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}. The value of the asymmetry amplitude sin2β\sin2\beta is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged B0B^0 decays in the CP-eigenstate modes. We find sin2β=0.59±0.14(stat)±0.05(syst)\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

    Measurement of the Branching Fraction for B- --> D0 K*-

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    We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

    Melanoma tumour vasculature heterogeneity: from mice models to human

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    Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3.106 SK-Mel-28 melanoma cells in C57BL/6 and nude mice, respectively. Tumour growth was evaluated weekly, while vasculature was analysed through fluorescent labelling via CD31 and desmin. Significant differences in tumour growth and mice survival were evidenced between the two melanoma models. A fast evolution of tumours was observed for B16F10 melanoma, reaching a tumour size of 100 mm3 in 7 days compared to SK-Mel-28 which needed 21 days to reach the same volumes. Important differences in vascularization were exposed between the melanoma models, characterized by a significant enhancement of vascular density and a significant lumen size for mice melanoma models compared to human. Immunostaining revealed irregularities in endothelium structure for both melanoma models, but structural differences of vasculature were observed, characterized by a stronger expression of desmin in SK-Mel-28 tumours. While human melanoma mainly develops capillaries, structural irregularities are also observed on the samples of this tumour model. Our study revealed an impact of cell type and tumour progression on the structural vasculature of melanoma, which could impact the distribution of drugs in the tumour environment
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