Temperature and pH Stimuli-Responsive System Delivers Location-Specific Antimicrobial Activity with Natural Products.

Smart materials with controlled stimuli-responsive functions are at the forefront of technological development. In this work, we present a generic strategy that combines simple components, physicochemical responses, and easy fabrication methods to achieve a dual stimuli-responsive system capable of location-specific antimicrobial cargo delivery. The encapsulated system is fabricated by combining a biocompatible inert polymeric matrix of poly(dimethylsiloxane) (PDMS) and a bioactive cargo of saturated fatty acids. We demonstrate the effectiveness of our approach to deliver antimicrobial activity for the model bacteria Escherichia coli. The system responds to two control variables, temperature and pH, delivering two levels of antimicrobial response under distinct combinations of stimuli: one response toward the planktonic media and another response directly at the surface for sessile bacteria. Spatially resolved Raman spectroscopy alongside thermal and structural material analysis reveals that the system not only exhibits ON/OFF states but can also control relocation and targeting of the active cargo toward either the surface or the liquid media, leading to different ON/OFF states for the planktonic and sessile bacteria. The approach proposed herein is technologically simple and scalable, facing low regulatory barriers within the food and healthcare sectors by using approved components and relying on fundamental chemical processes. Our results also provide a proof-of-concept platform for the design and easy fabrication of delivery systems capable of operating as Boolean logic gates, delivering different responses under different environmental conditions.

Nanoparticle-Imprinted Silica Gel for the Size-Selective Capture of Silver Ultrafine Nanoparticles from Water.

A synthetic approach has been developed to prepare silica gel monoliths that embed well separated silver or gold spherical nanoparticles (NP), with diameters of 8, 18 and 115 nm. Fe3+, O2/cysteine and HNO3 were all successfully used to oxidize and remove silver NP from silica, while aqua regia was necessary for gold NP. In all cases, NP-imprinted silica gel materials were obtained, with spherical voids of the same dimensions of the dissolved particles. By grinding the monoliths, we prepared NP-imprinted silica powders that were able to efficiently reuptake silver ultrafine NP (Ag-ufNP, d = 8 nm) from aqueous solutions. Moreover, the NP-imprinted silica powders showed a remarkable size selectivity, based on the best match between NP radius and the curvature radius of the cavities, driven by the optimization of attractive Van der Waals forces between SiO2 and NP. Ag-ufNP are increasingly used in products, goods, medical devices, disinfectants, and their consequent diffusion in the environment is of rising concern. Although limited here to a proof-of-concept level, the materials and methods described in this paper may be an efficient solution for capturing Ag-ufNP from environmental waters and to safely dispose them.

Effect of Local Topography on Cell Division of Staphylococcus spp.

Surface engineering is a promising strategy to limit or prevent the formation of biofilms. The use of topographic cues to influence early stages of biofilm formationn has been explored, yet many fundamental questions remain unanswered. In this work, we develop a topological model supported by direct experimental evidence, which is able to explain the effect of local topography on the fate of bacterial micro-colonies of Staphylococcus spp. We demonstrate how topological memory at the single-cell level, characteristic of this genus of Gram-positive bacteria, can be exploited to influence the architecture of micro-colonies and the average number of surface anchoring points over nano-patterned surfaces, formed by vertically aligned silicon nanowire arrays that can be reliably produced on a commercial scale, providing an excellent platform to investigate the effect of topography on the early stages of Staphylococcus spp. colonisation. The surfaces are not intrinsically antimicrobial, yet they delivered a topography-based bacteriostatic effect and a significant disruption of the local morphology of micro-colonies at the surface. The insights from this work could open new avenues towards designed technologies for biofilm engineering and prevention, based on surface topography.

A Novel Self-Assembly Strategy for the Fabrication of Nano-Hybrid Satellite Materials with Plasmonically Enhanced Catalytic Activity.

The generation of hydrogen from water using light is currently one of the most promising alternative energy sources for humankind but faces significant barriers for large-scale applications due to the low efficiency of existing photo-catalysts. In this work we propose a new route to fabricate nano-hybrid materials able to deliver enhanced photo-catalytic hydrogen evolution, combining within the same nanostructure, a plasmonic antenna nanoparticle and semiconductor quantum dots (QDs). For each stage of our fabrication process we probed the chemical composition of the materials with nanometric spatial resolution, allowing us to demonstrate that the final product is composed of a silver nanoparticle (AgNP) plasmonic core, surrounded by satellite Pt decorated CdS QDs (CdS@Pt), separated by a spacer layer of SiO2 with well-controlled thickness. This new type of photoactive nanomaterial is capable of generating hydrogen when irradiated with visible light, displaying efficiencies 300% higher than the constituting photo-active components. This work may open new avenues for the development of cleaner and more efficient energy sources based on photo-activated hydrogen generation.

Ion shuttling between emulsion droplets by crown ether modified gold nanoparticles.

Selective unidirectional transport of barium ions between droplets in a water-in-chloroform emulsion is demonstrated. Gold nanoparticles (GNPs) modified with a thiolated crown ether act as barium ion complexing shuttles that carry the ions from one population of droplets (source) to another (target). This process is driven by a steep barium ion concentration gradient between source and target droplets. The concentration of barium ions in the target droplets is kept low at all times by the precipitation of insoluble barium sulfate. A potential role of electrostatically coupled secondary processes that maintain the electroneutrality of the emulsion droplets is discussed. Charging of the GNP metal cores by electron transfer in the presence of the Fe(ii)/Fe(iii) redox couple appears to affect the partitioning of the GNPs between the water droplets and the chloroform phase. Processes have been monitored and studied by optical microscopy, Raman spectroscopy, cryogenic scanning electron microscopy (cryo-SEM) and zeta potential. The shuttle action of the GNPs has further been demonstrated electrochemically in a model system.

One-step preparation of antimicrobial silicone materials based on PDMS and salicylic acid: insights from spatially and temporally resolved techniques.

In this work, we introduce a one-step strategy that is suitable for continuous flow manufacturing of antimicrobial PDMS materials. The process is based on the intrinsic capacity of PDMS to react to certain organic solvents, which enables the incorporation of antimicrobial actives such as salicylic acid (SA), which has been approved for use in humans within pharmaceutical products. By combining different spectroscopic and imaging techniques, we show that the surface properties of PDMS remain unaffected while high doses of the SA are loaded inside the PDMS matrix. The SA can be subsequently released under physiological conditions, delivering a strong antibacterial activity. Furthermore, encapsulation of SA inside the PDMS matrix ensured a diffusion-controlled release that was tracked by spatially resolved Raman spectroscopy, Attenuated Total Reflectance IR (ATR-IR), and UV-Vis spectroscopy. The biological activity of the new material was evaluated directly at the surface and in the planktonic state against model pathogenic bacteria, combining confocal laser scanning microscopy, electron microscopy, and cell viability assays. The results showed complete planktonic inhibition for clinically relevant strains of Staphylococcus aureus and Escherichia coli, and a reduction of up to 4 orders of magnitude for viable sessile cells, demonstrating the efficacy of these surfaces in preventing the initial stages of biofilm formation. Our approach adds a new option to existing strategies for the antimicrobial functionalisation of a wide range of products such as catheters, wound dressings and in-dwelling medical devices based on PDMS.

Fast dissolution of silver nanoparticles at physiological pH.

While silver nanoparticles (AgNP) are used in topical treatments and medical devices for humans, no smooth, safe remedy exists to remove them and avoid possible post-treatment uptake in the body. We show here that cysteamine hydrochloride (CYS∙HCl), a simple FDA and EMA approved molecule, is able to dramatically accelerate the otherwise extremely slow oxidation of citrate-coated AgNP by O2 in a wide range of pH, including the physiological 7.4 value, obtaining the halving of AgNP concentration in t < 10 min. The dependence of oxidation kinetics on CYS concentration and pH is studied, finding faster processes on increasing CYS and basicity, despite the decrease of O2 reduction potential. Complexation and electrochemical studies demonstrate that CYS adhesion to AgNP surface followed by formation of 1:2 Ag+:CYS complex is the driving force for the AgNP oxidation, this also giving a definitive explanation to the otherwise still unclear phenomenon of AgNP etching by thiols. The efficacy of CYS∙HCl is verified also on AgNP coated with pectin and PEG-SH, and on AgNP immobilized on surfaces.

Exploiting Covalent, H-Bonding, and π-π Interactions to Design Antibacterial PDMS Interfaces That Load and Release Salicylic Acid.

Smart antimicrobial surfaces are a powerful tool to prevent bacterial colonization at surfaces. In this work, we report a successful strategy for the functionalization of polydimethylsiloxane (PDMS) surfaces, widely used in medical devices, with salicylic acid (SA), a biocide approved for use in humans. Antimicrobial PDMS surfaces were fabricated via a rational design in which bifunctional silane linker molecules were covalently grafted onto the PDMS via one end, while soft intermolecular interactions with SA were generated at the other end to enable reversible load and release of the biocide. A molecular level understanding of the interface was obtained using attenuated total reflectance Fourier transform infrared, Raman, and X-ray photoelectron spectroscopies, alongside density functional theory calculations. These reveal that the linker molecules dock the SA molecules at the surface via a 1:1 complexation interaction. Furthermore, each 1:1 complex acts as a nucleation point onto which multiple stacks of the biocide are subsequently stabilized via a combination of H-bonding and π-π stacking interactions, thus significantly enhancing SA uptake at the interface. The antimicrobial activity of these surfaces against model Gram-negative and Gram-positive bacteria represented by Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis is demonstrated by a log 6 reduction of planktonic bacterial populations and an efficient anti-biofilm activity at the surface.

Modular approach for bimodal antibacterial surfaces combining photo-switchable activity and sustained biocidal release.

Photo-responsive antibacterial surfaces combining both on-demand photo-switchable activity and sustained biocidal release were prepared using sequential chemical grafting of nano-objects with different geometries and functions. The multi-layered coating developed incorporates a monolayer of near-infrared active silica-coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This modular approach also enables us to unravel static and photo-activated contributions to the overall antibacterial performance of the surfaces, demonstrating a remarkable synergy between these two mechanisms. Complementary microbiological and imaging evaluations on both planktonic and surface-attached bacteria provided new insights on these distinct but cooperative effects.

Hydride formation thermodynamics and hysteresis in individual Pd nanocrystals with different size and shape.

Physicochemical properties of nanoparticles may depend on their size and shape and are traditionally assessed in ensemble-level experiments, which accordingly may be plagued by averaging effects. These effects can be eliminated in single-nanoparticle experiments. Using plasmonic nanospectroscopy, we present a comprehensive study of hydride formation thermodynamics in individual Pd nanocrystals of different size and shape, and find corresponding enthalpies and entropies to be nearly size- and shape-independent. The hysteresis observed is significantly wider than in bulk, with details depending on the specifics of individual nanoparticles. Generally, the absorption branch of the hysteresis loop is size-dependent in the sub-30 nm regime, whereas desorption is size- and shape-independent. The former is consistent with a coherent phase transition during hydride formation, influenced kinetically by the specifics of nucleation, whereas the latter implies that hydride decomposition either occurs incoherently or via different kinetic pathways.

The conquest of middle-earth: combining top-down and bottom-up nanofabrication for constructing nanoparticle based devices.

The development of top-down nanofabrication techniques has opened many possibilities for the design and realization of complex devices based on single molecule phenomena such as e.g. single molecule electronic devices. These impressive achievements have been complemented by the fundamental understanding of self-assembly phenomena, leading to bottom-up strategies to obtain hybrid nanomaterials that can be used as building blocks for more complex structures. In this feature article we highlight some relevant published work as well as present new experimental results, illustrating the versatility of self-assembly methods combined with top-down fabrication techniques for solving relevant challenges in modern nanotechnology. We present recent developments on the use of hierarchical self-assembly methods to bridge the gap between sub-nanometer and micrometer length scales. By the use of non-covalent self-assembly methods, we show that we are able to control the positioning of nanoparticles on surfaces, and to address the deterministic assembly of nano-devices with potential applications in plasmonic sensing and single-molecule electronics experiments.

Single-molecule electronics: from chemical design to functional devices.

The use of single molecules in electronics represents the next limit of miniaturisation of electronic devices, which would enable us to continue the trend of aggressive downscaling of silicon-based electronic devices. More significantly, the fabrication, understanding and control of fully functional circuits at the single-molecule level could also open up the possibility of using molecules as devices with novel, not-foreseen functionalities beyond complementary metal-oxide semiconductor technology (CMOS). This review aims at highlighting the chemical design and synthesis of single molecule devices as well as their electrical and structural characterization, including a historical overview and the developments during the last 5 years. We discuss experimental techniques for fabrication of single-molecule junctions, the potential application of single-molecule junctions as molecular switches, and general physical phenomena in single-molecule electronic devices.

A versatile self-assembly strategy for the synthesis of shape-selected colloidal noble metal nanoparticle heterodimers.

The self-assembly of individual nanoparticles into dimers-so-called heterodimers-is relevant for a broad range of applications, in particular in the vibrant field of nanoplasmonics and nanooptics. In this paper we report the synthesis and characterization of material- and shape-selected nanoparticle heterodimers assembled from individual particles via electrostatic interaction. The versatility of the synthetic strategy is shown by assembling combinations of metal particles of different shapes, sizes, and metal compositions like a gold sphere (90 nm) with either a gold cube (35 nm), gold rhombic dodecahedron (50 nm), palladium truncated cube (120 nm), palladium rhombic dodecahedron (110 nm), palladium octahedron (130 nm), or palladium cubes (25 and 70 nm) as well as a silver sphere (90 nm) with palladium cubes (25 and 70 nm). The obtained heterodimer combinations are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX), dynamic light scattering (DLS), and zeta-potential measurements. We describe the optimal experimental conditions to achieve the highest yield of heterodimers compared to other aggregates. The experimental results have been rationalized using theoretical modeling. A proof-of-principle experiment where individual Au-Pd heterodimers are exploited for indirect plasmonic sensing of hydrogen finally illustrates the potential of these structures to probe catalytic processes at the single particle level.

Antibacterial activity of glutathione-coated silver nanoparticles against Gram positive and Gram negative bacteria.

In the present paper, we study the mechanism of antibacterial activity of glutathione (GSH) coated silver nanoparticles (Ag NPs) on model Gram negative and Gram positive bacterial strains. Interference in bacterial cell replication is observed for both cellular strains when exposed to GSH stabilized colloidal silver in solution, and microbicidal activity was studied when GSH coated Ag NPs are (i) dispersed in colloidal suspensions or (ii) grafted on thiol-functionalized glass surfaces. The obtained results confirm that the effect of dispersed GSH capped Ag NPs (GSH Ag NPs) on Escherichia coli is more intense because it can be associated with the penetration of the colloid into the cytoplasm, with the subsequent local interaction of silver with cell components causing damages to the cells. Conversely, for Staphylococcus aureus, since the thick peptidoglycan layer of the cell wall prevents the penetration of the NPs inside the cytoplasm, the antimicrobial effect is limited and seems related to the interaction with the bacterial surfaces. Experiments on GSH Ag NPs grafted on glass allowed us to elucidate more precisely the antibacterial mechanism, showing that the action is reduced because of GSH coating and the limitation of the translational freedom of NPs.

Optical method for predicting the composition of self-assembled monolayers of mixed thiols on surfaces coated with silver nanoparticles.

With a simple optical method, based on UV-vis absorption spectra on glass slides, it is possible to predict the composition of self-assembled monolayers of mixed thiols, grafted on monolayers of silver nanoparticles. Glass slides are modified with the layer-by-layer technique, first forming a monolayer of mercaptopropyltrimethoxysilane, then grafting a monolayer of silver nanoparticles on it. These surfaces are further coated by single or mixed thiol monolayers, by dipping the slides in toluene solutions of the chosen thiols. Exchange constants are calculated for the competitive deposition between the colorless 1-dodecanethiol or PEG5000 thiol and BDP-SH, with the latter being a thiol-bearing molecule containing the strongly absorbing BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) moiety, synthesized on purpose. The constants are calculated by determining the fraction of BDP-SH deposited on the surface from a solution with a given molar fraction, directly measuring the absorption spectra of BDP-SH on the slides. Then, the exchange constant for the competitive deposition between 1-dodecanethiol and PEG5000 thiol is calculated by combining their exchange constants with BDP-SH. This allows to predict the fraction of the two colorless thiols coating the silver nanoparticles slides obtained from a toluene solution with a given molar fraction, for example, of PEG5000 thiol. The correctness of the calculated surface fraction is verified by studying the coating competition between 1-dodecanethiol and a PEG5000 thiol remotely modified with a strongly absorbing fluorescein fragment.

Synthesis, characterization and antibacterial activity against Gram positive and Gram negative bacteria of biomimetically coated silver nanoparticles.

In the present work, we describe a simple procedure to produce biomimetically coated silver nanoparticles (Ag NPs), based on the postfunctionalization and purification of colloidal silver stabilized by citrate. Two biological capping agents have been used (cysteine Cys and glutathione GSH). The composition of the capped colloids has been ascertained by different techniques and antibacterial tests on GSH-capped Ag NPs have been conducted under physiological conditions, obtaining values of Minimum Inhibitory Concentration (MIC) of 180 and 15 µg/mL for Staphylococcus aureus and Escherichia coli, respectively. The antibacterial activity of these GSH capped NPs can be ascribed to the direct action of metallic silver NPs, rather than to the bulk release of Ag(+).

Micelles as containers for self-assembled nanodevices: a fluorescent sensor for lipophilicity.

Potentiometric titrations, fluorescence versus pH titrations, dynamic light scattering and fluorescence polarization anisotropy studies demonstrate that inside the nanodimensioned Triton X-100 micelles, 1-pyrenecarboxylic acid, PCOO(-), forms an apical complex with the Zn(2+) cation encircled by a lipophilic cyclen ligand and hugely increasing its fluorescence. The ability of the Zn(2+)-cyclen-PCOO(-) complex plus its micellar container to act as a fluorescent sensor to evaluate the lipophilicity of molecular species is demonstrated on the fatty acid series CH(3)(CH(2))(x)COOH (x=0-16). At pH 7.4 a decrease in fluorescence is observed on the addition of fatty acids that is directly related to their chain length, that is, to their tendency to enter the micellar containers, where they dislocate PCOO(-) from the Zn(2+) centre. The independent determination of fatty acid pK(a) values in the presence of Triton X-100 micelles confirms that our fluorescent micellar device is capable of sensing their lipophilicity.