Tailoring Mesoporous Silica-Coated Silver Nanoparticles and Polyurethane-Doped Films for Enhanced Antimicrobial Applications.

The global increase in multidrug-resistant bacteria poses a challenge to public health and requires the development of new antibacterial materials. In this study, we examined the bactericidal properties of mesoporous silica-coated silver nanoparticles, varying the core sizes (ca. 28 nm and 51 nm). We also investigated gold nanoparticles (ca. 26 nm) coated with mesoporous silica as possible inert metal cores. To investigate the modification of antimicrobial activity after the surface charge change, we used silver nanoparticles with a silver core of 28 nm coated with a mesoporous shell (ca. 16 nm) and functionalized with a terminal amine group. Furthermore, we developed a facile method to create mesoporous silica-coated silver nanoparticles (Ag@mSiO2) doped films using polyurethane (IROGRAN®) as a polymer matrix via solution casting. The antibacterial effects of silver nanoparticles with different core sizes were analyzed against Gram-negative and Gram-positive bacteria relevant to the healthcare and food industry. The results demonstrated that gold nanoparticles were inert, while silver nanoparticles exhibited antibacterial effects against Gram-negative (Escherichia coli and Salmonella enterica subsp. enterica serovar Choleraesuis) and Gram-positive (Bacillus cereus) strains. In particular, the larger Ag@mSiO2 nanoparticles showed a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 18 µg/mL in the Salmonella strain. Furthermore, upon terminal amine functionalization, reversing the surface charge to positive values, there was a significant increase in the antibacterial activity of the NPs compared to their negative counterparts. Finally, the antimicrobial properties of the nanoparticle-doped polyurethane films revealed a substantial improvement in antibacterial efficacy. This study provides valuable information on the potential of mesoporous silica-coated silver nanoparticles and their applications in fighting multidrug-resistant bacteria, especially in the healthcare and food industries.

Bis(o-methylserotonin)-containing iridium(III) and ruthenium(II) complexes as new cellular imaging dyes: synthesis, applications, and photophysical and computational studies.

We report the synthesis, characterization, and scope of a new versatile emissive molecular probe functionalized with a 1,10-phenanthroline moiety containing methylserotonin groups as binding sites for metal ion recognition. The synthesis, characterization, and evaluation of the in vitro imaging capability of the iridium(III) and ruthenium(II) complexes [Ir(ppy)2(N-N)](+) and [Ru(bpy)2(N-N)](2+), in which ppy is 2-phenylpyridine, bpy is 2,2'-bipyridine, and N-N is a 1,10-phenanthroline ligand functionalized with two methylserotonin groups to serve as binding sites for metal ion recognition, is reported. The uptake of these compounds by living freshwater fish (Carassius auratus) was studied by fluorescence microscopy, and the cytotoxicity of ligand N-N and [Ru(bpy)2(N-N)](2+) in this species was also investigated.

Steady-state and time-resolved investigations on pyrene-based chemosensors.

Two novel fluorescent probes bearing a single (P) and two (a podand-like structure, L) pyrene units derived from 1,5-bis(2-aminophenoxy)-3-oxopentane have been synthesized and investigated in dioxane using UV-vis absorption, and steady-state and time-resolved (in a picosecond time scale) emission spectroscopy; in the gas phase, matrix-assisted laser desorption ionization mass spectrometry was employed. In dioxane, the absorption and emission spectra of P present a unique band with maxima at 361 and 392 nm, which have been associated with the monomer absorption and emission bands, respectively. In dioxane, for compound L, an additional band with a maximum at ∼525 nm is observed; upon the addition of water, an emissive band (with maxima varying from 405 to 490 nm) appears in both P and L spectra; this is discussed in terms of the emission of a species with charge character. Upon metal addition (Cu(2+), Zn(2+), and Ag(+)) to P, a gradual quenching effect of the monomer emission is observed and found to be more pronounced with Cu(2+). In the case of L, upon the addition of metal cations, the long emission band (∼550 nm) decreases and the monomer emission band increases (with an isoemissive point at ∼450 nm) and no evidence for the intermediate band (at ∼405-490 nm) now exists. Time-resolved data in dioxane/water mixtures showed that for P and L these two fit double- and triple-exponential decay laws, respectively. With P, this has been attributed to a two-state system, which involves the monomer and a charged species, with its emission maxima varying with the polarity of the media (here mirrored by its dielectric constant), which can potentially be addressed to an exciplex-like species, whereas with L, it has been attributed to a three-state system involving, in addition to these two species, an excimer. From absorption and fluorescence excitation and time-resolved data, evidence is given for the presence of intramolecular dimer formation in the ground state.

Corrole and corrole functionalized silica nanoparticles as new metal ion chemosensors: a case of silver satellite nanoparticles formation.

Corrole macrocycles are very appealing dyes for incorporation into light harvesting devices. This work shows the sensorial ability of 5,10,15-tris(pentafluorophenyl)corrole 1 and its monoanionic species toward Na(+), Ca(2+), Cu(2+), Cd(2+), Pb(2+), Hg(2+), Ag(+), and Al(3+) metal ions in toluene and acetonitrile. The photophysical studies toward metal ions were carried out by absorption and emission spectroscopy. From all metal ions studied, corrole 1 shows to be colorimetric for Hg(2+) allowing a naked-eye detection of Hg(2+) through a change of color from purple to blue in acetonitrile and from green to yellow in toluene. In addition a new ß-imine corrole 4 was successful synthesized and further functionalized with 3-isocyanatopropyl-trimethoxysilane resulting in an alkoxysilane derivative 5. The grafting of alkoxysilane derivative 5 with optically transparent silica nanoparticles (SiNPs) was achieved succesfully. The new-coated silica nanoparticles with corrole 5 were studied in the presence of Cu(2+), Hg(2+), and Ag(+) as metal ion probes. Interestingly, upon addition of Ag(+), groups of satellite AgNPs were formed around the SiNPs and were checked by transmission electron microscopy (TEM). At same time, a change of color from green to yellow was observed.

Synthesis and Structural Characterization of Branched Bimetallic AuPd Nanoparticles with a Highly Tunable Optical Response.

Bimetallic nanostructures composed of gold (Au) and palladium (Pd) have garnered increased interest for their applications in heterogeneous catalysis. This study reports a simple strategy for manufacturing Au@Pd bimetallic branched nanoparticles (NPs), which offer a tunable optical response, using polyallylamine-stabilized branched AuNPs as template cores for Pd overgrowth. The palladium content can be altered by manipulating the concentration of PdCl42- and ascorbic acid (AA) that are injected, which permit an overgrowth of the Pd shell up to ca. 2 nm thick. The homogeneous distribution of Pd at the surfaces of Au NPs can be carried out regardless of their size or branching degree, which allows for an adjustment of the plasmon response in the near-infrared (NIR) spectral range. As a proof of concept, the nanoenzymatic activity of pure gold and gold-palladium NPs was compared, exploring their peroxidase-like activity in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The bimetallic AuPd NPs demonstrate an increase in the catalytic properties attributed to the presence of palladium at the surface of gold.

Adenosine-Monophosphate-Assisted Homogeneous Silica Coating of Silver Nanoparticles in High Yield.

In this study, we propose a novel approach for the silica coating of silver nanoparticles based on surface modification with adenosine monophosphate (AMP). Upon AMP stabilization, the nanoparticles can be transferred into 2-propanol, promoting the growth of silica on the particle surfaces through the standard Stöber process. The obtained silica shells are uniform and homogeneous, and the method allows a high degree of control over shell thickness while minimizing the presence of uncoated NPs or the negligible presence of core-free silica NPs. In addition, AMP-functionalized AgNPs could be also coated with a mesoporous silica shell using cetyltrimethylammonium chloride (CTAC) as a template. Interestingly, the thickness of the mesoporous silica coating could be tightly adjusted by either the silica precursor concentration or by varying the CTAC concentration while keeping the silica precursor concentration constant. Finally, the influence of the silica coating on the antimicrobial effect of AgNPs was studied on Gram-negative bacteria (R. gelatinosus and E. coli) and under different bacterial growth conditions, shedding light on their potential applications in different biological environments.

Polyallylamine assisted synthesis of 3D branched AuNPs with plasmon tunability in the vis-NIR region as refractive index sensitivity probes.

This paper describes the synthesis of highly branched gold nanoparticles (AuNPs) through a facile seeded growth approach using poly(allylamine hydrochloride) (PAH) as shape inducing agent. The obtained branched AuNPs present highly tunable optical properties in the Vis-NIR region from ca. 560 nm to 1260 nm. We controlled the morphology, and therefore the optical response, of the NPs by either changing the gold salt to seeds ratio or by fine-tuning the solution pH. We proposed that the formation of size-dependent PAH-AuCl4- aggregates as demonstrated by dynamic light scattering measurements, together with pH-dependent gold salt speciation might be responsible for the branched morphology. Advanced electron microscopy techniques demonstrated the polycrystalline nature of the AuNPs and facilitated a better understanding of branched morphology. Additionally, the refractive index sensitivity estimated by the inflection point of the Localized Surface Plasmon Resonance (LSPR) band can be controlled by tuning the nanoparticle branching. Furthermore, the versatility of the PAH chemistry allowed the easy functionalization of the synthesized NPs.

Synthesis of Mesoporous Silica Coated Gold Nanorods Loaded with Methylene Blue and Its Potentials in Antibacterial Applications.

In this work, the successful preparation and characterization of gold nanorods (AuNRs) coated with a mesoporous silica shell (AuNRs@Simes) was achieved. Conjugation with methylene blue (MB) as a model drug using ultrasound-stimulated loading has been explored for further application in light-mediated antibacterial studies. Lyophilization of this conjugated nanosystem was analyzed using trehalose (TRH) as a cryogenic protector. The obtained stable dry formulation shows potent antimicrobial activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria after a simple post-treatment irradiation method with a red laser during a short time period.

Polymer Micro and Nanoparticles Containing B(III) Compounds as Emissive Soft Materials for Cargo Encapsulation and Temperature-Dependent Applications.

Polymer nanoparticles doped with fluorescent molecules are widely applied for biological assays, local temperature measurements, and other bioimaging applications, overcoming several critical drawbacks, such as dye toxicity, increased water solubility, and allowing imaging of dyes/drug delivery in water. In this work, some polymethylmethacrylate (PMMA), polyvinylpyrrolidone (PVP) and poly(styrene-butadiene-styrene) (SBS) based micro and nanoparticles with an average size of about 200 nm and encapsulating B(III) compounds have been prepared via the reprecipitation method by using tetrahydrofuran as the oil phase and water. The compounds are highly hydrophobic, but their encapsulation into a polymer matrix allows obtaining stable colloidal dispersions in water (3.39 µM) that maintain the photophysical behavior of these dyes. Although thermally activated non-radiative processes occur by increasing temperature from 25 to 80 °C, the colloidal suspension of the B(III) particles continues to emit greenish light (λ = 509 nm) at high temperatures. When samples are cooling back to room temperature, the emission is restored, being reversible. A probe of concept drug delivery study was conducted using coumarin 6 as a prototype of a hydrophobic drug.

Study and Preparation of Multifunctional Poly(L-Lysine)@Hyaluronic Acid Nanopolyplexes for the Effective Delivery of Tumor Suppressive MiR-34a into Triple-Negative Breast Cancer Cells.

Non-viral gene delivery using exogenous microRNAs is a potential strategy for fighting cancers with poor prognosis and which lack specific therapies, such as triple-negative breast cancer (TNBC). Herein we report the synthesis of six nontoxic electrostatic polymeric nanocapsules (P1 to P6) for microRNA delivery in TNBC cells. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM) were used to characterize the nanopolyplexes, synthesized with Poly(L-Lysine) and hyaluronic acid (Ha). Studies on the activity of the ternary HA/PLI/miRNA-34 nanopolyplexes towards TNBC cell line MDA-MB-231 were conducted. The nanopolyplexes mediated intracellular restoration of tumor suppressor miR34a was evaluated by using Western blotting to quantify the expression level of the Bcl-2 protein. The results suggest that the P5, with a ratio PLI/Ha of 0.05, was the most promising for the delivery of miR-34a into TNBC cells; the P5 nanocapsules were able to reduce Bcl-2 expression at a protein level, and had an effect in the overall cell viability after 24 h treatment.

Ultrasonic-assisted extraction and digestion of proteins from solid biopsies followed by peptide sequential extraction hyphenated to MALDI-based profiling holds the promise of distinguishing renal oncocytoma from chromophobe renal cell carcinoma.

A novel analytical approach is proposed to discriminate between solid biopsies of chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). The method comprises the following steps: (i) ultrasonic extraction of proteins from solid biopsies, (ii) protein depletion with acetonitrile, (iii) ultrasonic assisted in-solution digestion using magnetic nanoparticle with immobilized trypsin, (iv) C18 tip-based preconcentration of peptides, (v) sequential extraction of the peptides with ACN, (vi) MALDI-snapshot of the extracts and (vii) investigation of the extract containing the most discriminating features using high resolution mass spectrometry. With this approach we have been able to differentially cluster renal oncocytoma and chromophobe renal cell carcinoma and identified 18 proteins specific to chromophobe and seven unique to renal oncocytoma. Chromophobes express proteins associated with ATP function (ATP5I & 5E; VATE1 & G2; ADT2), glycolysis (PGK1) and neuromedin whilst oncocytomas express ATP5H, ATPA, DEPD7 and TRIPB thyroid receptor interacting protein.

Label-free protein quantification after ultrafast digestion of complex proteomes using ultrasonic energy and immobilized-trypsin magnetic nanoparticles.

The ultimate high-throughput, high robustness and easy-to-handling sample treatment method for label-free shotgun proteomics is presented in this work. It is based on joining the effectiveness of immobilized trypsin at the nanoscale level with the latest technology to deliver ultrasonic energy. The new method can be used to reduce sample preparation time comprising the steps of reduction, alkylation and digestion time to just 15 min without compromising shotgun label-free protein quantification. It is demonstrated that trypsin immobilized at the nano-scale performs better than the commercially available counterpart macroparticles. Considering the current advances in (i) ultrasonic energy delivery that allows 96 samples to be treated at once in 30 min, and (ii) chromatography and mass spectrometry for shotgun proteomics, that allow to analyze complex proteomes in 5 min, we envision this methodology as the universal one to digest complex proteomes as it allows to profile quantitatively more than 200 samples per day.

Exploring the Control in Antibacterial Activity of Silver Triangular Nanoplates by Surface Coating Modulation.

In the present work, the synthesis and characterization of silver triangular nanoplates (AgNTs) and their silica coating composites are reported. Engineering control on the surface coating has demonstrated the possibility to modulate the antibacterial effect. Several AgNT-coated nanomaterials, such as PVP (Polyvinylpyrrolidone) and MHA (16-mercaptohexadecanoic acid) as a stable organic coating system as well as uniform silica coating (≈5 nm) of AgNTs, have been prepared and fully characterized. The antibacterial properties of the systems reported, organic (MHA) and inorganic (amine and carboxylic terminated SiO2) coating nanocomposites, have been tested on Gram-positive and Gram-negative bacteria strains. We observed that the AgNTs' organic coating improved antimicrobial properties when compared to other spherical silver colloids found in the literature. We have also found that thick inorganic silica coating decreases the antimicrobial effect, but does not cancel it. In addition, the effect of surface charge in AgNTs@Si seems to play a crucial role toward S. aureus ATCC 25923 bacteria, obtaining MIC/MBC values compared to the AgNTs with an organic coating.

Synthesis of Gold Functionalised Nanoparticles with the Eranthis hyemalis Lectin and Preliminary Toxicological Studies on Caenorhabditis elegans.

The lectin found in the tubers of the Winter Aconite (Eranthis hyemalis) plant (EHL) is a Type II Ribosome Inactivating Protein (RIP). Type II RIPs have shown anti-cancer properties and have great potential as therapeutic agents. Similarly, colloidal gold nanoparticles are successfully used in biomedical applications as they can be functionalised with ligands with high affinity and specificity for target cells to create therapeutic and imaging agents. Here we present the synthesis and characterization of gold nanoparticles conjugated with EHL and the results of a set of initial assays to establish whether the biological effect of EHL is altered by the conjugation. Gold nanoparticles functionalised with EHL (AuNPs@EHL) were successfully synthesised by bioconjugation with citrate gold nanoparticles (AuNPs@Citrate). The conjugates were analysed by UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Zeta Potential analysis, and Transmission Electron Microscopy (TEM). Results indicate that an optimal functionalisation was achieved with the addition of 100 µL of EHL (concentration 1090 ± 40 µg/mL) over 5 mL of AuNPs (concentration [Au°] = 0.8 mM). Biological assays on the effect of AuNPs@EHL were undertaken on Caenorhabditis elegans, a free-living nematode commonly used for toxicological studies, that has previously been shown to be strongly affected by EHL. Citrate gold nanoparticles did not have any obvious effect on the nematodes. For first larval stage (L1) nematodes, AuNPs@EHL showed a lower biological effect than EHL. For L4 stage, pre-adult nematodes, both EHL alone and AuNPs@EHL delayed the onset of reproduction and reduced fecundity. These assays indicate that EHL can be conjugated to gold nanoparticles and retain elements of biocidal activity.

Green and Red Fluorescent Dyes for Translational Applications in Imaging and Sensing Analytes: A Dual-Color Flag.

Invited for this month's cover picture is the BIOSCOPE group of Professors Carlos Lodeiro and José Luis Capelo at the REQUIMTE/UCIBIO-LAQv-FCT University NOVA of Lisbon (Portugal), and their collaborators. The cover picture is devoted to Translational Research, and shows the Portuguese Flag represented by the interaction between cells and Janus gold/silver nanoparticles functionalized with rhodamine (red) and Fluorescein (green) dyes as tools for biomedical translational research. Read the full text of their Review at 10.1002/open.201700135.

Green and Red Fluorescent Dyes for Translational Applications in Imaging and Sensing Analytes: A Dual-Color Flag.

Red and green are two of the most-preferred colors from the entire chromatic spectrum, and red and green dyes are widely used in biochemistry, immunohistochemistry, immune-staining, and nanochemistry applications. Selective dyes with green and red excitable chromophores can be used in biological environments, such as tissues and cells, and can be irradiated with visible light without cell damage. This critical review, covering a period of five years, provides an overview of the most-relevant results on the use of red and green fluorescent dyes in the fields of bio-, chemo- and nanoscience. The review focuses on fluorescent dyes containing chromophores such as fluorescein, rhodamine, cyanine, boron-dipyrromethene (BODIPY), 7-nitobenz-2-oxa-1,3-diazole-4-yl, naphthalimide, acridine orange, perylene diimides, coumarins, rosamine, Nile red, naphthalene diimide, distyrylpyridinium, benzophosphole P-oxide, benzoresorufins, and tetrapyrrolic macrocycles. Metal complexes and nanomaterials with these dyes are also discussed.

Engineered Nanostructured Materials for Ofloxacin Delivery.

Antibiotic resistance is emerging as a growing worldwide problem and finding solutions to this issue is becoming a new challenge for scientists. As the development of new drugs slowed down, advances in nanotechnology offer great opportunities, with the possibility of designing new systems for carrying, delivery and administration of drugs already in use. Engineered combinations of the synthetic, broad-spectrum antibiotic ofloxacin, rarely studied in this field, with different types of silver, mesoporous silica-based and Pluronic/silica-based nanoparticles have been explored. The nanocarriers as silver core@silica mesoporous (AgMSNPs) and dye-doped silica nanoparticles functionalized with ofloxacin were synthesized and their antibacterial properties studied against S. aureus and E. coli. The best antibacterial results were obtained for the AgMSNPs nanosystem@ofloxacin for the strain S. aureus ATCC 25923, with MIC and MBC values of 5 and 25 µg/mL, proving the efficacy and synergetic effect of the antibiotic and the Ag core of the nanoparticles.

Supercritical CO2-Assisted Spray Drying of Strawberry-Like Gold-Coated Magnetite Nanocomposites in Chitosan Powders for Inhalation.

Lung cancer is one of the leading causes of death worldwide. Therefore, it is of extreme importance to develop new systems that can deliver anticancer drugs into the site of action when initiating a treatment. Recently, the use of nanotechnology and particle engineering has enabled the development of new drug delivery platforms for pulmonary delivery. In this work, POXylated strawberry-like gold-coated magnetite nanocomposites and ibuprofen (IBP) were encapsulated into a chitosan matrix using Supercritical Assisted Spray Drying (SASD). The dry powder formulations showed adequate morphology and aerodynamic performances (fine particle fraction 48%-55% and aerodynamic diameter of 2.6-2.8 µm) for deep lung deposition through the pulmonary route. Moreover, the release kinetics of IBP was also investigated showing a faster release of the drug at pH 6.8, the pH of lung cancer. POXylated strawberry-like gold-coated magnetite nanocomposites proved to have suitable sizes for cellular internalization and their fluorescent capabilities enable their future use in in vitro cell based assays. As a proof-of-concept, the reported results show that these nano-in-micro formulations could be potential drug vehicles for pulmonary administration.

Synthesis and Characterization of PtTe2 Multi-Crystallite Nanoparticles using Organotellurium Nanocomposites.

Herein, we report the synthesis of new PtTe2 multi-crystallite nanoparticles (NPs) in different sizes through an annealing process using new nanostructured Pt-Te organometallic NPs as a single source precursor. This precursor was obtained in a single reaction step using Ph2Te2 and H2PtCl6 and could be successfully size controlled in the nanoscale range. The resulting organometallic composite precursor could be thermally decomposed in 1,5 pentanediol to yield the new PtTe2 multi-crystallite NPs. The final size of the multi-crystallite spheres was successfully controlled by selecting the nanoprecursor size. The sizes of the PtTe2 crystallites formed using the large spheres were estimated to be in the range of 2.5-6.5 nm. The results provide information relevant to understanding specific mechanistic aspects related to the synthesis of organometallic nanomaterials and nanocrystals based on platinum and tellurium.

Single and combined effects of aluminum (Al2O3) and zinc (ZnO) oxide nanoparticles in a freshwater fish, Carassius auratus.

The increasing use of nanoparticles (NPs) worldwide has raised some concerns about their impact on the environment. The aim of the study was to assess the toxicity of metal oxide nanoparticles, singly or combined, in a freshwater fish (Carassius auratus). The fish were exposed for 7, 14, and 21 days to different concentrations of NPs (10 µg Al2O3.L-1, 10 µg ZnO.L-1, 10 µg Al2O3.L-1 plus 10 µg ZnO.L-1, 100 µg Al2O3.L-1, 100 µg ZnO.L-1, and 100 µg Al2O3.L-1 plus 100 µg ZnO.L-1). At the end of each exposure period, antioxidant enzyme activity (catalase, glutathione-S-transferase, and superoxide dismutase), lipid peroxidation, and histopathology were assessed in the gills and livers of C. auratus. The results show an increase in catalase (CAT) and superoxide dismutase (SOD) activity in the gills and livers of fish, especially after 14 days of exposure to single and combined NPs, followed by a reduction at 21 days. An increase in glutathione S-transferase (GST) was observed in gills after 7 days for all tested NP concentrations (single and combined); while in livers, a significant increase was determined after 14 days of exposure to 100 µg.L-1 of both single ZnO and Al2O3 NPs. Lipid peroxidation (LPO) significantly increased in gills after 7 days of exposure to 100 µg.L-1 Al2O3 NPs (single or combined). In livers, LPO increased significantly after 7 days of exposure to all tested concentrations of both single ZnO and Al2O3 (except for 10 µg Al2O3.L-1), and after 14 days of exposure to ZnO (10 and 100 µg.L-1) and Al2O3 (100 µg.L-1). The results from histological observations suggest that exposure to metal oxide NPs affected both livers and gills, presenting alterations such as gill hyperplasia and liver degeneration. However, the most pronounced effects were found in gills. In general, this study shows that the tested NPs, single or combined, are capable of causing sub-lethal effects on C. auratus, but when combined, NPs seem to be slightly more toxic than when added alone.