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1.
Anal Chem ; 95(49): 18287-18294, 2023 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-38044628

RESUMEN

Bacterial biofilms are structured communities consisting of cells enmeshed in a self-generated extracellular matrix usually attached to a surface. They contain diverse classes of molecules including polysaccharides, lipids, proteins, nucleic acids, and diverse small organic molecules (primary and secondary metabolites) which are organized to optimize survival and facilitate dispersal to new colonization sites. In situ characterization of the chemical composition and structure of bacterial biofilms is necessary to fully understand their development on surfaces relevant to biofouling in health, industry, and the environment. Biofilm development has been extensively studied using confocal microscopy using targeted fluorescent labels providing important insights into the architecture of biofilms. Recently, cryopreparation has been used to undertake targeted in situ chemical characterization using Orbitrap secondary ion mass spectrometry (OrbiSIMS), providing a label-free method for imaging biofilms in their native state. Although the high mass resolution of OrbiSIMS enables more confident peak assignments, it is still very challenging to assign most of the peaks in the spectra due to complexity of SIMS spectra and lack of automatic peak assignment methods. Here, we analyze the same OrbiSIMS depth profile data generated from the frozen-hydrated biofilm, but employ a new untargeted chemical filtering process utilizing mass spectral databases to assign secondary ions to decipher the large number of fragments present in the SIMS spectra. To move towards comprehensive analysis of different chemistries in the sample, we apply a molecular formula prediction approach which putatively assigns 81% of peaks in the 3D OrbiSIMS depth profile analysis. This enables us to catalog over 1000 lipids and their fragments, 3500 protein fragments, 71 quorum sensing-related molecules (2-alkyl-4-quinolones and N-acylhomoserine lactones), 150 polysaccharide fragments, and glycolipids simultaneously from one data set and map these separated molecular classes spatially through a Pseudomonas aeruginosa biofilm. Assignment of different chemistries in this sample facilitates identification of differences between biofilms grown on biofilm-promoting and biofilm-resistant polymers.


Asunto(s)
Biopelículas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/química , Percepción de Quorum , Espectrometría de Masa de Ion Secundario/métodos , Glucolípidos
2.
Small ; 19(22): e2300029, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36852650

RESUMEN

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting-two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing. In tumor invasive margin patient cells, the stimuli-responsive multifunctional NPs target GBM cells, enhance cell uptake by 12-fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long-term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli-responsive multifunctional NPs as an effective anti-GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Nanomedicina , Distribución Tisular , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Encéfalo , Barrera Hematoencefálica/patología , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Línea Celular Tumoral , Microambiente Tumoral
3.
Int J Mol Sci ; 24(21)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37958979

RESUMEN

Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. Staphylococcus aureus is both a human commensal and an opportunistic pathogen that colonizes human tissues and causes acute and chronic infections. Virulence and colonization factors are positively and negatively regulated, respectively, by bacterial cell-to-cell communication (quorum sensing) via the agr (accessory gene regulator) system. When cultured under low-shear modelled microgravity conditions (LSMMG), S. aureus has been reported to maintain a colonization rather than a pathogenic phenotype. Here, we show that the modulation of agr expression via reduced production of autoinducing peptide (AIP) signal molecules was responsible for this behavior. In an LSMMG environment, the S. aureus strains JE2 (methicillin-resistant) and SH1000 (methicillin-sensitive) both exhibited reduced cytotoxicity towards the human leukemia monocytic cell line (THP-1) and increased fibronectin binding. Using S. aureus agrP3::lux reporter gene fusions and mass spectrometry to quantify the AIP concentrations, the activation of agr, which depends on the binding of AIP to the transcriptional regulator AgrC, was delayed in the strains with an intact autoinducible agr system. This was because AIP production was reduced under these growth conditions compared with the ground controls. Under LSMMG, S. aureus agrP3::lux reporter strains that cannot produce endogenous AIPs still responded to exogenous AIPs. Provision of exogenous AIPs to S. aureus USA300 during microgravity culture restored the cytotoxicity of culture supernatants for the THP-1 cells. These data suggest that microgravity does not affect AgrC-AIP interactions but more likely the generation of AIPs.


Asunto(s)
Infecciones Estafilocócicas , Ingravidez , Humanos , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Staphylococcus aureus/metabolismo , Proteínas Quinasas/metabolismo , Percepción de Quorum/genética , Regulación hacia Abajo , Péptidos/metabolismo , Proteínas Bacterianas/metabolismo
4.
Anal Chem ; 94(11): 4703-4711, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35276049

RESUMEN

Modern mass spectrometry techniques produce a wealth of spectral data, and although this is an advantage in terms of the richness of the information available, the volume and complexity of data can prevent a thorough interpretation to reach useful conclusions. Application of molecular formula prediction (MFP) to produce annotated lists of ions that have been filtered by their elemental composition and considering structural double bond equivalence are widely used on high resolving power mass spectrometry datasets. However, this has not been applied to secondary ion mass spectrometry data. Here, we apply this data interpretation approach to 3D OrbiSIMS datasets, testing it for a series of increasingly complex samples. In an organic on inorganic sample, we successfully annotated the organic contaminant overlayer separately from the substrate. In a more challenging purely organic human serum sample we filtered out both proteins and lipids based on elemental compositions, 226 different lipids were identified and validated using existing databases, and we assigned amino acid sequences of abundant serum proteins including albumin, fibronectin, and transferrin. Finally, we tested the approach on depth profile data from layered carbonaceous engine deposits and annotated previously unidentified lubricating oil species. Application of an unsupervised machine learning method on filtered ions after performing MFP from this sample uniquely separated depth profiles of species, which were not observed when performing the method on the entire dataset. Overall, the chemical filtering approach using MFP has great potential in enabling full interpretation of complex 3D OrbiSIMS datasets from a plethora of material types.


Asunto(s)
Lípidos , Espectrometría de Masa de Ion Secundario , Bases de Datos Factuales , Humanos , Iones/química
5.
Mol Pharm ; 18(9): 3247-3259, 2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34399050

RESUMEN

We have employed a bespoke setup combining confocal Raman microscopy and an ultraviolet-visible (UV-Vis) spectroscopy flow cell to investigate the effect of excipients on the disproportionation kinetics of Pioglitazone HCl (PioHCl) in tablets during dissolution. Three binary formulations of PioHCl, containing citric acid monohydrate (CA), lactose monohydrate (LM), or magnesium stearate (MgSt), respectively, were used as models to study the influence of excipients' physicochemical properties on the rate of salt disproportionation kinetics and dissolution performance in different aqueous pH environments. It was found that formulation excipients can induce or prevent salt disproportionation by modulating the microenvironmental pH regardless of the pH of the dissolution media. Incorporating CA in PioHCl tablets preserves the salt form and enhances the dissolution performance of the salt in the acidic medium (pH = 1.2). In contrast, LM and MgSt had a detrimental effect on in vitro drug performance by inducing salt disproportionation in the tablet during dissolution in the same acidic medium. Dissolution in the neutral medium (pH = 6.8) showed rapid formation of the free base upon contact with the dissolution medium. The Raman maps of the cross-sectioned tablets revealed the formation of a shell consisting of the free base around the edge of the tablet. This shell decreased the rate of penetration of the dissolution medium into the tablet, which had significant implications on the release of the API into the surrounding solution, as shown by the UV-vis absorption spectroscopy drug release data. Our findings highlight the utility of the Raman/UV-vis flow cell analytical platform as an advanced analytical technique to investigate the effect of excipients and dissolution media on salt disproportionation in real time. This methodology will be used to enhance our understanding of salt stability studies that may pave the way for more stable multicomponent formulations.


Asunto(s)
Composición de Medicamentos/métodos , Excipientes/química , Pioglitazona/farmacocinética , Química Farmacéutica , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Pioglitazona/química , Sales (Química)/química , Solubilidad , Espectrometría Raman , Comprimidos
6.
Biotechnol Lett ; 41(1): 1-25, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30368691

RESUMEN

Bioreactors hold a lot of promise for tissue engineering and regenerative medicine applications. They have multiple uses including cell cultivation for therapeutic production and for in vitro organ modelling to provide a more physiologically relevant environment for cultures compared to conventional static conditions. Bioreactors are often used in combination with scaffolds as the nutrient flow can enhance oxygen and diffusion throughout the 3D constructs to prevent the formation of necrotic cores. A variety of scaffolds have been fabricated to achieve a structural architecture that mimic native extracellular matrix. Future developments of in vitro models will incorporate the ability to non-invasively monitor the cellular microenvironment to enhance the understanding of in vitro conditions. This review details current advancements in bioreactor and scaffold systems and provides insight on how in vitro models can be augmented for future biomedical applications.


Asunto(s)
Reactores Biológicos , Técnicas de Cultivo de Célula/instrumentación , Ingeniería de Tejidos/instrumentación , Animales , Técnicas de Cultivo de Célula/métodos , Humanos , Ingeniería de Tejidos/métodos
7.
Langmuir ; 33(20): 4924-4933, 2017 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-28459585

RESUMEN

Our ability to tailor the electronic properties of surfaces by nanomodification is paramount for various applications, including development of sensing, fuel cell, and solar technologies. Moreover, in order to improve the rational design of conducting surfaces, an improved understanding of structure/function relationships of nanomodifications and effect they have on the underlying electronic properties is required. Herein, we report on the tuning and optimization of the electrochemical properties of indium tin oxide (ITO) functionalized with single-walled carbon nanotubes (SWCNTs). This was achieved by controlling in situ grafting of aryl amine diazonium films on the nanoscale which were used to covalently tether SWCNTs. The structure/function relationship of these nanomodifications on the electronic properties of ITO was elucidated via time-of-flight secondary ion mass spectrometry and electrochemical and physical characterization techniques which has led to new mechanistic insights into the in situ grafting of diazonium. We discovered that the connecting bond is a nitro group which is covalently linked to a carbon on the aryl amine. The increased understanding of the surface chemistry gained through these studies enabled us to fabricate surfaces with optimized electron transfer kinetics. The knowledge gained from these studies allows for the rational design and tuning of the electronic properties of ITO-based conducting surfaces important for development of various electronic applications.

8.
Mol Pharm ; 13(3): 1166-75, 2016 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-26845251

RESUMEN

Because of its weakly acidic nature (pKa of 4.5), indomethacin presents an aqueous solubility that significantly increases when changing from acidic to neutral/alkaline pH (1.5 µg/mL at pH 1.2 and 105.2 µg/mL at pH 7.4). We have therefore investigated the impact of the dissolution medium pH on the dissolution performance of indomethacin:Kollidon VA64 extrudates. The impact of the drug loading on the dissolution properties of these systems was also examined (5%, 15%, 30%, 50%, 70%, and 90% drug loading). Time-resolved Raman spectroscopy along with in-line UV-vis spectrophotometry was employed to directly relate changes in dissolution behavior to physicochemical changes that occur to the extrudate during the test. The dissolution tests were performed in pH 2 HCl (to mimic the stomach conditions), and this was then switched during the experiment to pH 6.8 phosphate buffer (to simulate the poststomach conditions). The rotating disc dissolution rate test was also used to simultaneously measure the dissolution rate of both the drug and the polymer. We found that in pH 2 HCl buffer, for the 15% or higher drug-loaded extrudates, Kollidon VA64 preferentially dissolves from the exterior of the compact leaving an amorphous drug-rich hydrophobic shell, which, similarly to an enteric coating, inhibits the drug release. The in situ formation of an enteric coating has been previously hypothesized, and this has been the first time that is directly observed in a pH-variable dissolution test. The dissolution medium switch to pH 6.8 phosphate buffer, due to the large increase of the aqueous solubility of indomethacin at this pH, leads to rapid dissolution of the material forming the coating and therefore total drug release. In contrast, the 5% extrudate is fully hydrated and quickly dissolves at low pH pointing to a dissolution performance dependent on highly water-soluble Kollidon VA64.


Asunto(s)
Preparaciones de Acción Retardada , Liberación de Fármacos , Excipientes/química , Indometacina/química , Polímeros/química , Pirrolidinas/química , Compuestos de Vinilo/química , Química Farmacéutica , Estabilidad de Medicamentos , Humanos , Concentración de Iones de Hidrógeno , Indometacina/metabolismo , Polímeros/metabolismo , Pirrolidinas/metabolismo , Espectrometría Raman , Compuestos de Vinilo/metabolismo , Agua/química
9.
Mol Pharm ; 12(5): 1512-22, 2015 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-25872658

RESUMEN

Real-time in situ Raman mapping has been employed to monitor, during dissolution, the crystallization transitions of amorphous bicalutamide formulated as a molecular dispersion in a copovidone VA64 matrix. The dissolution performance was also investigated using the rotating disc dissolution rate methodology, which allows simultaneous determination of the dissolution rate of both active ingredient and polymer. The dissolution behavior of two bicalutamide:copovidone VA64 dispersion formulations, containing 5% (w/w) and 50% (w/w) bicalutamide, respectively, was investigated, with the aim of exploring the effect of increasing the bicalutamide loading on the dissolution performance. Spatially time-resolved Raman maps generated using multivariate curve resolution indicated the simultaneous transformation of amorphous bicalutamide present in the 50% drug-loaded extrudate into metastable polymorphic form II and low-energy polymorphic form I. Fitting a kinetic model and spatially correlating the data extracted from the Raman maps also allowed us to understand the re-crystallization mechanisms by which the low-energy form I appears. Form I was shown to crystallize mainly directly from the amorphous solid dispersion, with crystallization from the metastable form II being a minor contribution.


Asunto(s)
Anilidas/química , Nitrilos/química , Compuestos de Tosilo/química , Cristalización , Cinética , Difracción de Polvo , Solubilidad , Espectrometría Raman
10.
Molecules ; 20(9): 16404-18, 2015 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-26378506

RESUMEN

We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Espectroscopía de Protones por Resonancia Magnética/métodos , Anilidas/química , Química Farmacéutica , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Nitrilos/química , Compuestos de Tosilo/química
11.
Sens Actuators B Chem ; 192: 126-133, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25844025

RESUMEN

A custom designed microelectromechanical systems (MEMS) micro-hotplate, capable of operating at high temperatures (up to 700 °C), was used to thermo-optically characterize fluorescent temperature-sensitive nanosensors. The nanosensors, 550 nm in diameter, are composed of temperature-sensitive rhodamine B (RhB) fluorophore which was conjugated to an inert silica sol-gel matrix. Temperature-sensitive nanosensors were dispersed and dried across the surface of the MEMS micro-hotplate, which was mounted in the slide holder of a fluorescence confocal microscope. Through electrical control of the MEMS micro-hotplate, temperature induced changes in fluorescence intensity of the nanosensors was measured over a wide temperature range. The fluorescence response of all nanosensors dispersed across the surface of the MEMS device was found to decrease in an exponential manner by 94%, when the temperature was increased from 25 °C to 145 °C. The fluorescence response of all dispersed nanosensors across the whole surface of the MEMS device and individual nanosensors, using line profile analysis, were not statistically different (p < 0.05). The MEMS device used for this study could prove to be a reliable, low cost, low power and high temperature micro-hotplate for the thermo-optical characterisation of sub-micron sized particles. The temperature-sensitive nanosensors could find potential application in the measurement of temperature in biological and micro-electrical systems.

13.
PLoS Negl Trop Dis ; 16(6): e0010531, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35675260

RESUMEN

[This corrects the article DOI: 10.1371/journal.pntd.0005971.].

14.
Analyst ; 136(9): 1799-801, 2011 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-21416087

RESUMEN

Ratiometric pH nanosensors with tuneable pK(a) were prepared by entrapping combinations of two pH-sensitive fluorophores (fluorescein isothiocyanate dextran (FITC-D) and Oregon Green(®) dextran (OG-D)) and a reference fluorophore (5-(and-6)-carboxytetramethylrhodamine dextran (TAMRA-D)), in a biocompatible polymer matrix. Dual-fluorophore pH nanosensors permit the measurement of an extended dynamic range, from pH 4.0 to 7.5.


Asunto(s)
Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Ionóforos , Polímeros/química , Materiales Biocompatibles/metabolismo , Dextranos/química , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Concentración de Iones de Hidrógeno , Nanopartículas/química , Nanotecnología
15.
Analyst ; 136(1): 29-41, 2011 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-20877821

RESUMEN

Nanoparticulate systems in various unique configurations are highly effective at detecting protease activity both in vivo and in vitro. In this article, we have summarised the conventional modern methods for monitoring protease activity, and critically appraised recent advances in protease-responsive nanosensors.


Asunto(s)
Técnicas Biosensibles/métodos , Endopeptidasas/química , Nanopartículas/química , Transferencia Resonante de Energía de Fluorescencia , Colorantes Fluorescentes/química , Proteínas Fluorescentes Verdes/química , Polímeros/química , Puntos Cuánticos , Espectrometría Raman
16.
NPJ Biofilms Microbiomes ; 7(1): 50, 2021 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-34140515

RESUMEN

Understanding the dynamic environmental microniches of biofilms will permit us to detect, manage and exploit these communities. The components and architecture of biofilms have been interrogated in depth; however, little is known about the environmental microniches present. This is primarily because of the absence of tools with the required measurement sensitivity and resolution to detect these changes. We describe the application of ratiometric fluorescent pH-sensitive nanosensors, as a tool, to observe physiological pH changes in biofilms in real time. Nanosensors comprised two pH-sensitive fluorophores covalently encapsulated with a reference pH-insensitive fluorophore in an inert polyacrylamide nanoparticle matrix. The nanosensors were used to analyse the real-time three-dimensional pH variation for two model biofilm formers: (i) opportunistic pathogen Pseudomonas aeruginosa and (ii) oral pathogen Streptococcus mutans. The detection of sugar metabolism in real time by nanosensors provides a potential application to identify therapeutic solutions to improve oral health.


Asunto(s)
Biopelículas , Técnicas Biosensibles , Concentración de Iones de Hidrógeno , Nanotecnología , Resinas Acrílicas/química , Biopelículas/crecimiento & desarrollo , Colorantes Fluorescentes/química , Glucosa/metabolismo , Nanopartículas/química , Permeabilidad , Pseudomonas/crecimiento & desarrollo , Pseudomonas/metabolismo , Imagen de Lapso de Tiempo
17.
Life (Basel) ; 11(2)2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540536

RESUMEN

Immune dysfunction has long been reported by medical professionals regarding astronauts suffering from opportunistic infections both during their time in space and a short period afterwards once back on Earth. Various species of prokaryotes onboard these space missions or cultured in a microgravity analogue exhibit increased virulence, enhanced formation of biofilms, and in some cases develop specific resistance for specific antibiotics. This poses a substantial health hazard to the astronauts confined in constant proximity to any present bacterial pathogens on long space missions with a finite number of resources including antibiotics. Furthermore, some bacteria cultured in microgravity develop phenotypes not seen in Earth gravity conditions, providing novel insights into bacterial evolution and avenues for research. Immune dysfunction caused by exposure to microgravity may increase the chance of bacterial infection. Immune cell stimulation, toll-like receptors and pathogen-associated molecular patterns can all be altered in microgravity and affect immunological crosstalk and response. Production of interleukins and other cytokines can also be altered leading to immune dysfunction when responding to bacterial infection. Stem cell differentiation and immune cell activation and proliferation can also be impaired and altered by the microgravity environment once more adding to immune dysfunction in microgravity. This review elaborates on and contextualises these findings relating to how bacteria can adapt to microgravity and how the immune system subsequently responds to infection.

18.
Biosensors (Basel) ; 11(7)2021 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-34356709

RESUMEN

Enteroviruses are ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and oligonucleotides to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral nucleic acid sequence (23 bases), which was identified through in silico screening. Oligonucleotides were designed to demonstrate specific complementarity towards the target enteroviral nucleic acid to produce aggregated gold-oligonucleotide nanoconstructs. The conserved target enteroviral nucleic acid sequence (≥1 × 10-7 M, ≥1.4 × 10-14 g/mL) initiates gold-oligonucleotide nanoconstruct disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow assays that utilise gold-oligonucleotide nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (<60 s), and could be interpreted with a bespoke software and hardware electronic interface. We anticipate that our methodology will translate in silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave the way forward in the clinical evaluation of disease and complement existing strategies to overcome antimicrobial resistance.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Ácidos Nucleicos , Oro/química , Humanos , Nanopartículas del Metal/química , Hibridación de Ácido Nucleico , Oligonucleótidos
19.
Photochem Photobiol Sci ; 9(6): 801-11, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20463998

RESUMEN

Reactive oxygen species (ROS) have for some time been implicated in the onset and progression of medical conditions including cancer, ageing, heart disease and Alzheimer's disease. Recently, it has been postulated that ROS play a much more subtle role in intracellular signalling mechanisms as second messengers. Given the importance of these species in influencing cellular processes, it is surprising that tools for studying intracellular levels of ROS are extremely limited and devices for studying the cells' response to internally generated ROS are virtually non-existent. In order to study the response of cells to intracellular ROS we have designed a nano-scale device that can both generate ROS and simultaneously monitor the cells' reaction as a function of changes in the important signalling ion, calcium. Here we report the synthesis, characterisation, and calibration of a new ROS nano-probe and demonstrate its ability to detect cellular response to elevated levels of intracellular ROS.


Asunto(s)
Nanopartículas/química , Porfirinas/química , Especies Reactivas de Oxígeno/química , Resinas Acrílicas/química , Técnicas Biosensibles , Calcio/química , Línea Celular , Humanos , Especies Reactivas de Oxígeno/metabolismo , Sistemas de Mensajero Secundario , Transducción de Señal
20.
J Control Release ; 327: 397-405, 2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-32798639

RESUMEN

Biologic therapeutics are the medicines of the future and are destined to transform the approaches by which the causes and symptoms of diseases are cured and alleviated. These approaches will be accelerated through the development of novel strategies that target multiple pharmacologically active sites using a combination of different biologics, or mixtures of biologics and small molecule therapeutics. However, for this potential to be realised, advancements in co-formulation strategies for biologic therapeutics must be established. This review describes the current and emerging developments within this field and highlights the challenges and potential solutions, that will pave-the-way towards their clinical translation.


Asunto(s)
Productos Biológicos
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