Thermoactive Smart Electrospun Nanofibers.

The recent burst of research on smart materials is a clear evidence of the growing interest of the scientific community, industry, and society in the field. The exploitation of the great potential of stimuli-responsive materials for sensing, actuation, logic, and control applications is favored and supported by new manufacturing technologies, such as electrospinning, that allows to endow smart materials with micro- and nanostructuration, thus opening up additional and unprecedented prospects. In this wide and lively scenario, this article systematically reviews the current advances in the development of thermoactive electrospun fibers and textiles, sorting them, according to their response to the thermal stimulus. Hence, several platforms including thermoresponsive systems, shape memory polymers, thermo-optically responsive systems, phase change materials, thermoelectric materials, and pyroelectric materials, are described and critically discussed. The difference in active species and outputs of the aforementioned categories is highlighted, evidencing the transversal nature of temperature stimulus. Moreover, the potential of novel thermoactive materials are pointed out, revealing how their development could take to utmost interesting achievements.

Photoluminescence-Based Techniques for the Detection of Micro- and Nanoplastics.

The growing numbers related to plastic pollution are impressive, with ca. 70 % of produced plastic (>350 tonnes/year) being indiscriminately wasted in the environment. The most dangerous forms of plastic pollution for biota and human health are micro- and nano-plastics (MNPs), which are ubiquitous and more bioavailable. Their elimination is extremely difficult, but the first challenge is their detection since existing protocols are unsatisfactory for microplastics and mostly absent for nanoplastics. After a discussion of the state of the art for MNPs detection, we specifically revise the techniques based on photoluminescence that represent very promising solutions for this problem. In this context, Nile Red staining is the most used strategy and we show here its pros and limitations, but we also discuss other more recent approaches, such as the use of fluorogenic probes based on perylene-bisimide and on fluorogenic hyaluronan nanogels, with the added values of biocompatibility and water solubility.

Static quenching upon adduct formation: a treatment without shortcuts and approximations.

Luminescence quenching is a process exploited in transversal applications in science and technology and it has been studied for a long time. The luminescence quenching mechanisms are typically distinguished in dynamic (collisional) and static, which can require different quantitative treatments. This is particularly important - and finds broad and interdisciplinary application - when the static quenching is caused by the formation of an adduct between the luminophore - at the ground state - and the quencher. Due to its nature, this case should be treated starting from the well-known law of mass action although, in specific conditions, general equations can be conveniently reduced to simpler ones. A proper application of simplified equations, though, can be tricky, with frequent oversimplifications taking to severe errors in the interpretation of the photophysical data. This tutorial review aims to (i) identify the precise working conditions for the application of the simplified equations of static quenching and to (ii) provide general equations for broadest versatility and applicability. The latter equations can be used even beyond the sole case of pure quenching, i.e., in the cases of partial quenching and even luminescence turn-on. Finally, we illustrate different applications of the equations via a critical discussion of examples in the field of sensing, supramolecular chemistry and nanotechnology.

Nitroxides as Building Blocks for Nanoantioxidants.

Nitroxides are an important class of radical trapping antioxidants whose promising biological activities are connected to their ability to scavenge peroxyl (ROO•) radicals. We have measured the rate constants of the reaction with ROO• (kinh) for a series of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) derivatives as 5.1 × 106, 1.1 × 106, 5.4 × 105, 3.7 × 105, 1.1 × 105, 1.9 × 105, and 5.6 × 104 M-1 s-1 for -H, -OH, -NH2, -COOH, -NHCOCH3, -CONH(CH2)3CH3, and ═O substituents in the 4 position, with a good Marcus relationship between log (kinh) and E° for the R2NO•/R2NO+ couple. Newly synthesized Pluronic-silica nanoparticles (PluS) having nitroxide moieties covalently bound to the silica surface (PluS-NO) through a TEMPO-CONH-R link and coumarin dyes embedded in the silica core, has kinh = 1.5 × 105 M-1 s-1. Each PluS-bound nitroxide displays an inhibition duration nearly double that of a structurally related "free" nitroxide. As each PluS-NO particle bears an average of 30 nitroxide units, this yields an overall ≈60-fold larger inhibition of the PluS-NO nanoantioxidant compared to the molecular analogue. The implications of these results for the development of novel nanoantioxidants based on nitroxide derivatives are discussed, such as the choice of the best linkage group and the importance of the regeneration cycle in determining the duration of inhibition.

In-Depth Study of the Electronic Properties of NIR-Emissive κ3N Terpyridine Rhenium(I) Dicarbonyl Complexes.

The structure-properties relationship in a series of carbonyl rhenium(I) complexes based on substituted terpyridine ligands of general formula [Re(κxN-Rtpy)(CO)yL]n+ is explored by both experimental and theoretical methods. In these compounds, the terpyridine ligands adopt both bidentate (κ2N) and terdentate (κ3N) coordination modes associated with three or two carbonyls, respectively. Conversion from the κ2N to the κ3N coordination mode leads to large changes in the absorption spectra and oxidation potentials due to destabilization of the HOMO level of each complex. The absorption profiles of the κ3N complexes cover the whole visible spectra with lower maxima around 700 nm, tailing out to 800 nm, while no emission is observed with Br- as the axial ligand L. When the axial ligand is modified from the native halide to pyridine or triphenylphosphine, the lowest absorption band is blue-shifted by 60 and 90 nm, respectively. These cationic complexes are near-infrared emitters with emission maxima between 840 and 950 nm for the pyridine compounds and 780-800 nm for the triphenylphosphine compounds.

Tandem Dye-Doped Nanoparticles for NIR Imaging via Cerenkov Resonance Energy Transfer.

The detection of the Cerenkov radiation (CR) is an emerging preclinical imaging technique which allows monitoring the in vivo distribution of radionuclides. Among its possible advantages, the most interesting is the simplicity and cost of the required instrumentation compared, e.g., to that required for PET scans. On the other hand, one of its main drawbacks is related to the fact that CR, presenting the most intense component in the UV-vis region, has a very low penetration in biological tissues. To address this issue, we present here multifluorophoric silica nanoparticles properly designed to efficiently absorb the CR radiation and to have a quite high fluorescence quantum yield (0.12) at 826 nm. Thanks to a highly efficient series of energy transfer processes, each nanoparticle can convert part of the CR into NIR light, increasing its detection even under 1.0-cm thickness of muscle.

Specific, Surface-Driven, and High-Affinity Interactions of Fluorescent Hyaluronan with PEGylated Nanomaterials.

Hybrid nanomaterials are a subject of extensive research in nanomedicine, and their clinical application is reasonably envisaged in the near future. However, the fate of nanomaterials in biological environments poses serious limitations to their application; therefore, schemes to monitor them and gain control on their toxicity could be of great help for the development of the field. Here, we propose a probe for PEGylated nanosurfaces based on hyaluronic acid (HA) functionalized with rhodamine B (RB). We show that the high-affinity interaction of this fluorogenic hyaluronan (HA-RB) with nanoparticles exposing PEGylated surfaces results in their sensing, labeling for super-resolution imaging, and synergistic cellular internalization. HA-RB forms nanogels that interact with high affinity-down to the picomolar range-with silica nanoparticles, selectively when their surface is covered by a soft and amphiphilic layer. This surface-driven interaction triggers the enhancement of the luminescence intensity of the dyes, otherwise self-quenched in HA-RB nanogels. The sensitive labeling of specific nanosurfaces also allowed us to obtain their super-resolution imaging via binding-activated localization microscopy (BALM). Finally, we show how this high-affinity interaction activates a synergistic cellular uptake of silica nanoparticles and HA-RB nanogels, followed by a differential fate of the two partner nanomaterials inside cells.

PluS Nanoparticles Loaded with Sorafenib: Synthetic Approach and Their Effects on Endothelial Cells.

Silica nanostructures are widely investigated for theranostic applications since relatively mild and easy synthetic methods allow the fabrication of multicompartment nanoparticles (NPs) and fine modulation of their properties. Here, we report the optimization of a synthetic strategy leading to brightly fluorescent silica NPs with a high loading ability, up to 45 molecules per NP, of Sorafenib, a small molecule acting as an antiangiogenic drug. We demonstrate that these NPs can efficiently release the drug and they are able to inhibit endothelial cell proliferation and migration and network formation. Their lyophilization can endow them with long shelf stability, whereas, once in solution, they show a much slower release compared to analogous micellar systems. Interestingly, Sorafenib released from Pluronic silica NPs completely prevented endothelial cell responses and postreceptor mitogen-activated protein kinase signaling ignited by vascular endothelial growth factor, one of the major players of tumor angiogenesis. Our results indicate that these theranostic systems represent a promising structure for anticancer applications since NPs alone have no cytotoxic effect on cultured endothelial cells, a cell type to which drugs and exogenous material are always in contact once delivered.

Optimized synthesis of luminescent silica nanoparticles by a direct micelle-assisted method.

Silica nanoparticles (NPs) are versatile nanomaterials, which are safe with respect to biomedical applications, and therefore are highly investigated. The advantages of NPs include their ease of preparation, inexpensive starting materials and the possibility of functionalization or loading with various doping agents. However, the solubility of the doping agent(s) imposes constraints on the choice of the reaction system and hence limits the range of molecules that can be included in the interior of NPs. To overcome this problem, herein, we improved the current state of the art synthetic strategy based on Pluronic F127 by enabling the synthesis in the presence of large amounts of organic solvents. The new method enables the preparation of nanoparticles doped with large amounts of water-insoluble doping agents. To illustrate the applicability of the technology, we successfully incorporated a range of phosphorescent metalloporphyrins into the interior of NPs. The resulting phosphorescent nanoparticles may exhibit potential for biological oxygen sensing.

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.

Mapping heterogeneous polarity in multicompartment nanoparticles.

Understanding polarity gradients inside nanomaterials is essential to capture their potential as nanoreactors, catalysts or in drug delivery applications. We propose here a method to obtain detailed, quantitative information on heterogeneous polarity in multicompartment nanostructures. The method is based on a 2-steps procedure, (i) deconvolution of complex emission spectra of two solvatochromic probes followed by (ii) spectrally resolved analysis of FRET between the same solvatochromic dyes. While the first step yields a list of polarities probed in the nanomaterial suspension, the second step correlates the polarities in space. Colocalization of polarities falling within few nanometer radius is obtained via FRET, a process called here nanopolarity mapping. Here, Prodan and Nile Red are tested to map the polarity of a water-dispersable, multicompartment nanostructure, named PluS nanoparticle (NPs). PluS NPs are uniform core-shell nanoparticles with silica cores (diameter ~10 nm) and Pluronic F127 shell (thickness ~7 nm). The probes report on a wide range of nanopolarities among which the dyes efficiently exchange energy via FRET, demonstrating the coexistence of a rich variety of environments within nanometer distance. Their use as a FRET couple highlights the proximity of strongly hydrophobic sites and hydrated layers, and quantitatively accounts for the emission component related to external water, which remains unaffected by FRET processes. This method is general and applicable to map nanopolarity in a large variety of nanomaterials.

Dual-Mode, Anisotropy-Encoded, Ratiometric Fluorescent Nanosensors: Towards Multiplexed Detection.

A nanosensor with dual-mode fluorescence response to pH and an encoded identification signal, was developed by exploiting excitation energy transfer and tailored control of molecular organization in core-shell nanoparticles. Multiple signals were acquired in a simple single-excitation dual-emission channels set-up.

Highly Sensitive, Anisotropic, and Reversible Stress/Strain-Sensors from Mechanochromic Nanofiber Composites.

Mechanochromic polymeric systems are intensively investigated for real-time stress detection applications. However, an effective stress-sensing material must respond to low deformation with a detectable color change that should be quickly reversible upon force unloading. In this work, mechanochromic nanofibers made by electrospinning are used to produce mechanochromic nanofiber/poly(dimethylsiloxane) (PDMS) composites with isotropic and anisoptropic response. Due to chain alignment of spiropyran copolymer chains within the nanofibers, only very small strains are required to yield a mechanochromic response. Composites with aligned and isotropic nanofibers show anisotropic and isotropic mechanochromic behavior, respectively. Due to the special substitution pattern of spiropyran in the copolymer, the mechanochromic response of these nanofiber/PDMS composites shows fast reversibility upon force unloading. The outstanding benefit of using highly sensitive mechanochromic nanofibers as filler in composite materials allows the detection of directional stress and strain, and it is a step forward in the development of smart, mechanically responsive materials.

A Fluorescent Sensor Array Based on Heteroatomic Macrocyclic Fluorophores for the Detection of Polluting Species in Natural Water Samples.

The development of a novel all-solid-state optical sensor array based on heteroatomic macrocyclic fluorophores (diaza-crown ether, metallocorrole and pyridinophans) for the photographic analysis of liquid media, is presented. The sensitivity of the new optical system toward a number of different species (cations: Li+, K+, Na+, NH4+ , Mg2+, Ca2+, Co2+, Cu2+, Zn2+, Cd2+, Pb2+ and anions: NO2- , NO3- , Cl-, Br-, HCO3- ) was evaluated both in single selective sensor mode and in multisensory arrangement. The satisfactory PLS1 regression models between sensor array optical response and analyte concentration were obtained for Cd2+, Cu2+, Zn2+, and NO2- ions in all the range of tested concentrations. Among these species the highest attention was focused onto detection of cadmium and nitrite ions, for which the detection limits, DL, estimated by 3σ method were found 0.0013 mg/L and 0.21 mg/L respectively, and these values are lower than the corresponding WHO guideline values of 0.003 mg/L (Cd2+) and 2 mg/L ( NO2- ). The suitability of the developed sensors implemented with familiar devices for signal acquisition (Light Emitting Diode, LED, as light source and a digital camera as a signal detector), and chemometric methods for data treatment to perform fast and low-cost monitoring of species under interest, in real samples of environmental importance, is demonstrated.

The Role of Onium Salts in the Pro-Oxidant Effect of Gold Nanoparticles in Lipophilic Environments.

Metal nanoparticles are reported to be toxic due to the generation of free radicals at their surface. Relatively inert thiol-capped gold nanoparticles (AuNPs) have been reported to induce radical formation in the presence of hydroperoxides, which would conflict with their potential use as inert scaffolds for the design of novel nano-antioxidants. With the aim of clarifying this aspect, we investigated the pro-oxidant activity of dodecanethiol-capped AuNPs (∼5 nm diameter), prepared through the Brust-Schiffrin synthesis, by oxygen-uptake kinetic studies. The pro-oxidant activity was found to be proportional to the impurities of the transfer agent tetraoctylammonium bromide (TOAB) left from the synthesis and decreased on repeated washing of the nanoparticles. Under identical settings similar batches of AuNP (∼9 nm diameter) prepared through the Ulman method without onium salts showed no pro-oxidant behavior. The alternative onium phase-transfer agents Oct4 NBF4 (Oct=octyl), Hex4 NBF4 (Hex=hexyl), and Hex4 NPF6 were comparatively investigated and showed lower pro-oxidant activity depending on the counterion (Br- >PF6- >BF4- ).

Non-enzymatic portable optical sensors for microcystin-LR.

We present here the development of an all-solid-state optical sensor based on phenyl-substituted diaza-18-crown-6 hydroxyquinoline (DCHQ-Ph) for the indirect selective detection of microcystin-LR (MC-LR), reaching a very low detection limit of 0.05 µg L-1, well below the World Health Organisation (WHO) guideline value (1 µg L-1) in potable water. We demonstrate the potential applicability of the developed method in fast and low-cost water toxicity estimation.

NIR-fluorescent dye doped silica nanoparticles for in vivo imaging, sensing and theranostic.

The development of nanostructures devoted to in vivo imaging and theranostic applications is one of the frontier fields of research worldwide. In this context, silica nanoparticles (SiO2-NPs) offer unquestionable positive properties: silica is intrinsically non-toxic, several versatile and accessible synthetic methods are available and many variations are possible, both in terms of porosity and functionalization for delivery and targeting purposes, respectively. Moreover, the accumulation of several dyes within a single nanostructure offers remarkable possibilities to produce very bright and photostable luminescent nanosystems. Advancements in imaging technology, bioassay, fluorescent molecular probes have boosted the efforts to develop dye doped fluorescent SiO2-NPs, but despite this, only a quite limited set of systems are applicable in vivo. Herein we discuss selected examples that appeared in the literature between 2013-17, with imaging capabilities in vivo and characterized by a significant near infrared (NIR) fluorescence emission. We present here very promising strategies to develop SiO2-NPs for diagnostic and therapeutic applications-some of which are already in clinical trials-and the possibility to develop bio-erodable SiO2-NPs. We are convinced that all these findings will be the basis for the spread of SiO2-NPs into clinical use in the near future.

Synthesis of a highly Mg2+-selective fluorescent probe and its application to quantifying and imaging total intracellular magnesium.

Magnesium plays a crucial role in many physiological functions and pathological states. Therefore, the evolution of specific and sensitive tools capable of detecting and quantifying this element in cells is a very desirable goal in biological and biomedical research. We developed a Mg2+-selective fluorescent dye that can be used to selectively detect and quantify the total magnesium pool in a number of cells that is two orders of magnitude smaller than that required by flame atomic absorption spectroscopy (F-AAS), the reference analytical method for the assessment of cellular total metal content. This protocol reports itemized steps for the synthesis of the fluorescent dye based on diaza-18-crown-6-hydroxyquinoline (DCHQ5). We also describe its application in the quantification of total intracellular magnesium in mammalian cells and the detection of this ion in vivo by confocal microscopy. The use of in vivo confocal microscopy enables the quantification of magnesium in different cellular compartments. As an example of the sensitivity of DCHQ5, we studied the involvement of Mg2+ in multidrug resistance in human colon adenocarcinoma cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin, and found that the concentration was higher in LoVo-R cells. The time frame for DCHQ5 synthesis is 1-2 d, whereas the use of this dye for total intracellular magnesium quantification takes 2.5 h and for ion bioimaging it takes 1-2 h.

Visible and Near-IR Emissions from k2 N- and k3 N-Terpyridine Rhenium(I) Assemblies Obtained by an [n×1] Head-to-Tail Bonding Strategy.

An [n×1] head-to-tail bonding strategy has been used for the synthesis of ReI metallacycles. From a k3 N-dicarbonyl precursor, a single discrete [4×1] square assembly was isolated and characterized, whereas a k2 N-tricarbonyl precursor led to two major species, a square and a [3×1] triangular assembly. Solid-state X-ray diffraction study has confirmed the high angular distortion (71° to 96°) of the k2 N precursors. The electrochemical reversibility of the triangular (5) and square (6, 7) assemblies is increased with respect to that of their precursors. Photophysical investigation has confirmed pronounced red-shifts in the emissions of the k3 N-dicarbonyl species 4 (935 nm) and 7 (980 nm), as confirmed by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations.

Naturally Inspired Molecules as Multifunctional Agents for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Aß protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic and therapeutic strategies aimed at preventing Aß generation and oxidative stress may represent an effective approach for AD treatment. A recent paradigm for the treatment of complex diseases such as AD suggests the employment of multifunctional compounds, single chemical entities capable of simultaneously modulating different targets involved in the pathology. In this paper, the "pharmacophores combination" strategy was applied, connecting the main scaffold of the BACE-1 ligand 1 to that of the chalcone 2, as metal chelating pharmacophore, to obtain a small library of compounds. Conjugate 5 emerged as the most interesting derivative, proving to inhibit BACE-1 with low-micromolar potency, and showing neuroprotective effects. In particular, 5 proved to be able to protect from metal-associated oxidative stress by hampering intracellular Cu(2+)-induced ROS formation without any direct neurotoxic effect.