Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of epsilon-poly-L-lysine capped mesoporous silica-based nanoparticles

[EN] Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into epsilon-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr(-)) permeability barrier for the HKAIs. The observed bactericidal activity against Gr(-) bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr(-) and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria. (C) 2016 Elsevier Inc. All rights reserved.This work was funded by FP7 ITN STARS-Scientific Training in Antimicrobial Research Strategies (Contract No. PITN-GA-2009-238490, J.M.W., A.M.), H2020 MSCA IF (AND-659121, N.V.), grant BIO2013-42619-P from the Ministerio de Economia y Competitividad (A.M.), grant from the Spanish Government (Project MAT2015-64139-C4-1-R,N. M., J.R.M, R.M.M.), and a grant from Generalitat Valenciana (Project PROMETEOII/2014/047, N.M.). and Prometeo II/2014/029, A.M.).Velikova, N.; Mas Font, N.; Miguel-Romero, L.; Polo, L.; Stolte, E.; Zaccaria, E.; Cao, R.... (2017). Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of epsilon-poly-L-lysine capped mesoporous silica-based nanoparticles. Nanomedicine Nanotechnology Biology and Medicine. 13(2):569-581. https://doi.org/10.1016/j.nano.2016.09.011S56958113

Pochopení mechanistické perspektivy při snímání energetických nitrosloučenin prostřednictvím spektroskopických a elektrochemických studií

Understanding the probable mechanism of detection plays a significant role in selecting a particular fluorophore for the detection of the complicated and low volatile analyte namely, nitroaromatic and non-aromatic high energy materials (HEMs) in the development of detection devices when compared with the existing techniques. The fluorescence quenching employing conducting polymers-based response of HEMs have attained great significance in recent times. Amongst all conducting polymers, functionalized polyaniline can act as a fluorophore in quenching studies. This report also reveals the importance of studying electrochemical methods associated with the changes observed in the oxidation potential and its resemblance with fluorescence quenching study in establishing the probable mechanism associated with the sensing study of HEMs (viz., RDX, PETN, CL-20 and RDX: CL-20 Cocrystal). FTIR and resonance Raman characterization helped us to understand the interaction between nitro groups present in HEMs with benzenoid unit or polaronic or bipolaronic nitrogen of camphor sulfonic acid doped polyaniline (CSA[PANi]). Employing Stern Volmer plot, the efficiency of quenching and quenching mechanisms of complex structure formed between the fluorophore and HEMs is understood.Pochopení pravděpodobného mechanismu detekce hraje významnou roli v tom. při výběru konkrétního fluoroforu pro detekci komplikovaných a nízkých koncentrací. těkavých analytů, konkrétně nitroaromatických a nearomatických vysokoenergetických materiálů. (HEM) při vývoji detekčních zařízení ve srovnání se stávajícími technikami. V poslední době dosáhlo velkého významu zhášení fluorescence s využitím reakce HEM na bázi vodivých polymerů. Ze všech vodivých polymerů může jako fluorofor ve zhášecích studiích působit funkcionalizovaný polyanilin. Tato zpráva také odhaluje význam studia elektrochemických metod spojených se změnami pozorovanými u oxidačního potenciálu a jejich podobnost se studiem zhášení fluorescence v prostředí stanovení pravděpodobného mechanismu spojeného se studiem detekce HEM (tj. RDX, PETN, CL-20 a RDX: CL-20 Cocrystal). FTIR a rezonanční Ramanova charakterizace nám pomohly pochopit interakci mezi nitroskupinami přítomnými v HEM s benzenovou jednotkou nebo polaronovým či bipolaronovým dusíkem polyanilinu dopovaného kyselinou kafrosulfonovou (CSA[PANi]). Pomocí Sternova Volmerova grafu byla zjištěna a pochopena účinnost zhášení a mechanismy zhášení komplexní struktury vytvořené mezi luoforem a HEMs

Tailored cancer therapy by magnetic nanoparticle hyperthermia: A virtual scenario simulation method

Background and objective: Hyperthermia is a cancer treatment aiming to induce cell death by directly warming cancerous tissues above 40 °C. This technique can be applied both individually and together with other cancer therapies. The main challenge for researchers and medics is to heat only tumoral cells avoiding global or localized heating of sane tissues. The objective in this study is to provide a realistic virtual scenario to develop an optimized multi-site injection plan for tailored magnetic nanoparticle-mediated hyperthermia applications. Methods: A three-dimensional model of a cat's back was tested in three different simulation scenarios, showing the impact of magnetic nanoparticles in each specific environment configuration. Results: As a result of this study. This simulation method can, minimising the affection to healthy tissue. Conclusions: This virtual method will help real and personalized therapy planning and tailor the dose and distribution of magnetic nanoparticles for an enhanced hyperthermia cancer treatment.ISSN:0169-2607ISSN:1872-756