Neutralization of ionic interactions by dextran-based single-chain nanoparticles improves tobramycin diffusion into a mature biofilm

The extracellular matrix protects biofilm cells by reducing diffusion of antimicrobials. Tobramycin is an antibiotic used extensively to treat P. aeruginosa biofilms, but it is sequestered in the biofilm periphery by the extracellular negative charge matrix and loses its efficacy significantly. Dispersal of the biofilm extracellular matrix with enzymes such as DNase I is another promising therapy that enhances antibiotic diffusion into the biofilm. Here, we combine the charge neutralization of tobramycin provided by dextran-based single-chain polymer nanoparticles (SCPNs) together with DNase I to break the biofilm matrix. Our study demonstrates that the SCPNs improve the activity of tobramycin and DNase I by neutralizing the ionic interactions that keep this antibiotic in the biofilm periphery. Moreover, the detailed effects and interactions of nanoformulations with extracellular matrix components were revealed through time-lapse imaging of the P. aeruginosa biofilms by laser scanning confocal microscopy with specific labeling of the different biofilm components

Technological challenges in the preclinical development of an HIV nanovaccine candidate

Despite a very active research in the field of nanomedicine, only a few nano-based drug delivery systems have reached the market. The “death valley” between research and commercialization has been partially attributed to the limited characterization and reproducibility of the nanoformulations. Our group has previously reported the potential of a peptide-based nanovaccine candidate for the prevention of SIV infection in macaques. This vaccine candidate is composed of chitosan/dextran sulfate nanoparticles containing twelve SIV peptide antigens. The aim of this work was to rigorously characterize one of these nanoformulations containing a specific peptide, following a quality-by-design approach. The evaluation of the different quality attributes was performed by several complementary techniques, such as dynamic light scattering, nanoparticle tracking analysis, and electron microscopy for particle size characterization. The inter-batch reproducibility was validated by three independent laboratories. Finally, the long-term stability and scalability of the manufacturing technique were assessed. Overall, these data, together with the in vivo efficacy results obtained in macaques, underline the promise this new vaccine holds with regard to its translation to clinical trialsThis work was supported by the European Union’s Horizon 2020 research program (NanoPilot project – grant agreement number 646142) and by Xunta de Galicia’s Grupos de referencia competitiva (grant number ED431C 2017/09). T.G. Dacoba acknowledges a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sports (grant number FPU14/05866)S

Synthesis of type II beta-turn surrogate dipeptides based on syn-alfa-amino-alfa, beta-dialkyl-beta-lactams

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochemical determinant of the α-alkylation reaction in β-branched α-phenyloxazolidinyl- or α-diphenyloxazolidinyl-β-lactams and provides the first stereocontrolled access to syn-α-amino-α,β-dialkyl(aryl)-β-lactams. These products are readily transformed into type II β-turn mimetic surrogates 2B.This work was supported by Spanish Ministerio de Educación y Ciencia (MEC; Project BQU2002-01737). Grants from Gobierno Vasco to A.B. and I.L. and from European Commission (Marie Curie HMPT-CT-2000-00173) to R.M.F., A.M., and K.R.P. are acknowledged.Peer reviewe

Synthesis of type II beta-turn surrogate dipeptides based on syn-alfa-amino-alfa, beta-dialkyl-beta-lactams. Supporting Information

Preparation procedures and physical and spectroscopic data for compounds 17−43 and crystallographic data in CIF format and ORTEP diagrams of 28 and 30.Peer reviewe

Electronic detection of DNA hybridization

Trabajo presentado al Congreso NanoSpain, celebrado del 14 al 18 de abril de 2008 en Braga (Portugal).Peer reviewe

Electronic detection of biomolecules by carbon nanotube field effect transistors

Resumen del trabajo presentado al Internantional Meeting on the Chemistry of Nanotubes: Science and Applications (ChemonTubes), celebrado en Zaragoza del 6 al 9 de abril de 2008.Peer reviewe

New route to polymeric nanoparticles by click chemistry using bifunctional cross-linkers

Trabajo presentado al Modern Trends in Polymer Science (EPF'09) celebrado en Graz (Austria) del 12 al 17 de Julio de 2009.A new route to functional polymeric nanoparticles (PNPs) of different chemical nature in the 3 to 20 nm size range is reported by combining both radical addition fragmentation chain transfer (RAFT) polymerization and “click” chemistry (CC) techniques. RAFT polymerization was employed for the synthesis of well-defined statistical copolymers with pending –Cl groups along the macromolecular chain. After transformation of the –Cl groups to –N3 groups by treatment with sodium azide, an appropriate bifunctional cross-linker is employed to obtain PNPs under CC conditions promoting intramolecular cycloaddition (cross-linking). Following this new route, polystyrene, poly(alkyl (meth)acrylate), polymethacrylic acid, poly(sodium styrenesulfonate) and poly(N-isopropyl) NPs have been synthesized and in-deep characterized.Financial support by MEC (Grant No. CSD2006-53, CIC NANOGUNECONSOLIDER) and Basque Government (i-Nanogune and CIC Biomagune-2008 Projects) is gratefully acknowledged.Peer reviewe

Label-free DNA biosensors based on functionalized carbon nanotube field effect transistors

A carbon nanotube transistor array was used to detect DNA hybridization. A new approach to ensure specific adsorption of DNA to the nanotubes was developed. The polymer poly (methylmethacrylate0.6-co-poly(ethyleneglycol)methacrylate0.15-co-N-succinimidyl methacrylate0.25) was synthesized and bonded noncovalently to the nanotube. Aminated single-strand DNA was then attached covalently to the polymer. After hybridization, statistically significant changes were observed in key transistor parameters. Hybridized DNA traps both electrons and holes, possibly caused by the charge-trapping nature of the base pairs.This work has been supported in part by the Spanish MEC project NAN2004-09415-C05-05/ and by the Molecular Foundry LBNL, Project 126. The devices have been fabricated in UC Berkeley’s Microlab. Work at the Molecular Foundry was supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The authors also thank MARCO/MSD for financial support.Peer reviewe