Gold Nanoparticles Decorated with Sialic Acid Terminated Bi-antennary N-Glycans for the Detection of Influenza Virus at Nanomolar Concentrations

Gold nanoparticles decorated with full-length sialic acid terminated complex bi-antennary N-glycans, synthesized with glycans isolated from egg yolk, were used as a sensor for the detection of both recombinant hemagglutinin (HA) and whole influenza A virus particles of the H1N1 subtype. Nanoparticle aggregation was induced by interaction between the sialic acid termini of the glycans attached to gold and the multivalent sialic acid binding sites of HA. Both dynamic light scattering (DLS) and UV/Vis spectroscopy demonstrated the efficiency of the sensor, which could detect viral HA at nanomolar concentrations and revealed a linear relationship between the extent of nanoparticle aggregation and the concentration of HA. UV/ Vis studies also showed that these nanoparticles can selectively detect an influenza A virus strain that preferentially binds sialic acid terminated glycans with a(2!6) linkages over a strain that prefers glycans with terminal a(2!3)-linked sialic acids

Effective targeting of DC-sign by α-fucosylamide functionalized gold nanoparticles

Dendritic Cells (DCs), the most potent antigenpresenting cells, play a critical role in the detection of invading pathogens, which are recognized also by multiple carbohydrate-specific receptors. Among them, DC-SIGN is one of the best characterized, with high-mannose and Lewis-type glycan specificity. In this study, we present a potent DC-SIGN targeting device developed using gold nanoparticles functionalized with \u3b1-fucosyl-\u3b2-alanyl amide. The nanoparticles bound to cellular DC-SIGN and induced internalization as effectively as similar particles coated with comparable amounts of LewisX oligosaccharide. They were found to be neutral toward dendritic cell maturation and IL-10 production, thus envisaging a possible use as targeted imaging tools and antigen delivery devices

Edge atoms effects on the perpendicular anisotropy of ultrathin magnetic layers

The present work reports experimental and theoretical results for electrodeposited Co/Au(111) ultrathin layers with very specific magnetic behavior. We show that the observed two peaks in the out-of-plane magnetization versus deposition time variation could be explained by the remarkably high perpendicular anisotropy of the perimeter atoms of low-dimensional islands formed during the layer-by-layer growth, as compared to that of the surface atoms. Our results indicate that it is possible to sustain high anisotropy in very small grains without coming across the superparamagnetic limit, opening excellent opportunities for materials engineering

Edge atoms effects on the perpendicular anisotropy of ultrathin magnetic layers

The present work reports experimental and theoretical results for electrodeposited Co/Au(111) ultrathin layers with very specific magnetic behavior. We show that the observed two peaks in the out-of-plane magnetization versus deposition time variation could be explained by the remarkably high perpendicular anisotropy of the perimeter atoms of low- dimensional islands formed during the layer-by-layer growth, as compared to that of the surface atoms. Our results indicate that it is possible to sustain high anisotropy in very small grains without coming across the superparamagnetic limit, opening excellent opportunities for materials engineering

Nature of magnetism in thiol-capped gold nanoparticles investigated with Muon spin rotation

© 2018 Author(s). Muon spin rotation/relaxation measurements show clear evidence for magnetism in 2.2 nm gold nanoparticles capped with butanethiol. At low temperatures (1.8 K), there is significant spin relaxation which decreases as a function of both the applied longitudinal magnetic field and increasing temperature. The results indicate that there are spatially inhomogeneous electronic moments that fluctuate with a wide distribution of correlation times. Possible explanations are discussed

Metal-based nanoparticles for combating antibiotic resistance

The resistance to antibiotics in combating bacteria is a serious worldwide problem. The search for new approaches to address antibacterial resistance is therefore of crucial importance and seeking alternatives for the treatment and control of bacterial diseases associated with resistant strains, which is in need of urgent action. There is an ongoing interest in metal-based nanoparticles (MBNPs) and their usage synergy with antibiotics due to their unique properties, such as overcoming bacterial resistance, reducing acute toxicity compared to their sizes, and allowing dosage reduction of active pharmaceutical ingredients. Combining MBNPs and antibiotics not only enhances the antibacterial effect but also allows the inhibition of biofilm production. Furthermore, MBNPs and antibiotics incorporated in polymeric biomaterial matrix have been widely studied to improve their efficiency and devoid the resistance. However, these studies need to be combined in a literature review. Polymeric biomaterials offer high mechanical stability with improved biocompatibility. Moreover, their use makes a single dose of administration of the final product with extended antibiotic half-life possible while slowly releasing their reservoir, which is an advantage in continuously combating resistance. This review focuses on different promising biomedical strategies for enhancing the bactericidal efficacy of antibiotics by the synergistic use of MBNPs, antibiotics, and polymeric biomaterials together to combat the resistance of different bacterial strains. In addition, it is prospected to guide opportunities for new research for future biomedical applications

Preparation and immunogenicity of gold glycol-nanoparticles as anti-pneumococcal vaccine model

Capsular polysaccharides (CPS) of encapsulated bacteria are critical determinants of bacterial virulence and have been used in the development of protective conjugate vaccines. Nanomaterials loaded with carbohydrate antigens are emerging as promising synthetic vaccine candidates, alternative to classic polysaccharide/protein conjugate vaccines. Repetitive antigen display, the ability to potentiate immune responses through enhanced antigen delivery to the immune system and the possibility to tune the loading of well-defined carbohydrates on different scaffolds are key factors supporting nanotechnology-based vaccines. Moreover, other structures can be incorporated onto the nanosystems as active mediators to increase vaccine efficacy. In this context, gold glyco-nanoparticles (GNPs) functionalized with the synthetic tetrasaccharide repeating unit of Streptococcus pneumoniae serotype 14 (Pn14PS), and the peptide fragment OVA323-339, serving as a T-helper epitope, have been demonstrated as able to elicit in vivo specific and functional IgG antibodies against native Pn14PS, thus promoting uptake and killing of bacteria Pn14.[1] Herein, we report the preparation and immunological evaluation of new GNPs containing two synthetic CPS fragments related to serotypes 19F and 14 of Streptococcus pneumoniae (Tri-19F and Tetra-14) simultaneously displayed on nanoparticle surface, together with the T-helper peptide fragment OVA323-339. We aimed to explore the effect of these GNPs, coated with different antigen patterns, on the immunological response in mice and whether this response is affected by the presence of both saccharide antigens from diverse bacterial serotypes loaded onto the same nanoparticle. The main goal of this study was to determine whether these GNPs could induce specific antibodies against CPSs of both pneumococcal serotypes 14 and 19F or to affect the immune activity of either of them. Mice immunization showed that the concomitant presence of Tri-19F and Tetra-14 on the same nanoparticle critically enhanced the titers of specific IgG antibodies towards type 14 polysaccharide compared to GNP exclusively displaying Tetra-14. We also found that the bi-antigenic GNPs induced anti-Pn14PS IgG antibodies titers of the same order of magnitude as the currently used PCV13 human vaccine

Synthesis of asparagine derivatives harboring a Lewis X type DC-SIGN ligand and evaluation of their impact on immunomodulation in multiple sclerosis

The protein myelin oligodendrocyte glycoprotein (MOG) is a key component of myelin and an autoantigen in the disease multiple sclerosis (MS). Post‐translational N‐glycosylation of Asn31 of MOG seems to play a key role in modulating the immune response towards myelin. This is mediated by the interaction of Lewis‐type glycan structures in the N‐glycan of MOG with the DC‐SIGN receptor on dendritic cells (DCs). Here, we report the synthesis of an unnatural Lewis X (LeX)‐containing Fmoc‐SPPS‐compatible asparagine building block (SPPS=solid‐phase peptide synthesis), as well as asparagine building blocks containing two LeX‐derived oligosaccharides: LacNAc and Fucα1‐3GlcNAc. These building blocks were used for the glycosylation of the immunodominant portion of MOG (MOG31‐55) and analyzed with respect to their ability to bind to DC‐SIGN in different biological setups, as well as their ability to inhibit the citrullination‐induced aggregation of MOG31‐55. Finally, a cytokine secretion assay was carried out on human monocyte‐derived DCs, which showed the ability of the neoglycopeptide decorated with a single LeX to alter the balance of pro‐ and anti‐inflammatory cytokines, inducing a tolerogenic response.Bio-organic Synthesi

Gold nanoparticles as carriers of streptococcus pneumoniae carbohydrate antigens fully synthetic vaccines

In the last years, gold nanoparticles have been largely evaluated as multivalent systems bearing biomolecules, thanks to their peculiarities. In particular, gold nanoparticles functionalized with (oligo)saccharides (gold glyconanoparticles, GNPs) have been developed in order to mimic the natural presentation of the carbohydrate coating which is present at the cell or pathogen surface. They are non-cytotoxic, soluble in biological media and easy to prepare and purify. Recently, GNPs coated with the tetrasaccharide Gal(\u3b21-4)Glc(\u3b21-6)[Gal(\u3b21-4)]\u3b2GlcNAc repeating unit of Streptococcus pneumoniae (SP) 14 capsular polysaccharide, OVA323-339 peptide as T helper cell, and \u3b2-D-glucoside to assist water solubility, in different molar ratio, were developed as synthetic conjugate vaccine4. The GNP bearing SP14/Glc/OVAp in 45:50:5 ratio resulted in the most active, able to induce IgG antibodies against native polysaccharide of S. Pneumoniae serotype 14. According to this result, we decided to prepare different GNPs bearing an analogue of the trisaccharide repeating unit ManNAc(\u3b21-4)Glc(\u3b11-2)Rha(\u3b11-OPO3-\u2192) of the 19F serotype of S. pneumoniae, alone or together with the tetrasaccharide of serotype 14. The idea is to develop new multiantigenic systems displaying different carbohydrate antigens arranged on a single nanoparticle. To prepare these GNPs, we have first synthesized the analogue of the trisaccharide antigen and a \u3b2-D-glucoside suitably functionalized with a thiol-ending linker in order to load them on the gold surface. The GNPs obtained, have been characterized by Transmission Electron Microscopy (TEM), Ultraviolet-Visible (UV/Vis), Circular Dichroism (CD), and Nuclear Magnetic Resonance (NMR). They show an exceptionally small core and uniform dispersion. Also, they are well soluble and stable in water. All the GNPs herein reported will be tested in vivo in mice to evaluate their ability to induce specific IgG antibodies against native capsular polysaccharide of S. pneumoniae type 14 and 19F