Data-Driven Predetermination of Cu Oxidation State in Copper Nanoparticles: Application to the Synthesis by Laser Ablation in Liquid.

Copper-based nanocrystals are reference nanomaterials for integration into emerging green technologies, with laser ablation in liquid (LAL) being a remarkable technique for their synthesis. However, the achievement of a specific type of nanocrystal, among the whole library of nanomaterials available using LAL, has been until now an empirical endeavor based on changing synthesis parameters and characterizing the products. Here, we started from the bibliographic analysis of LAL synthesis of Cu-based nanocrystals to identify the relevant physical and chemical features for the predetermination of copper oxidation state. First, single features and their combinations were screened by linear regression analysis, also using a genetic algorithm, to find the best correlation with experimental output and identify the equation giving the best prediction of the LAL results. Then, machine learning (ML) models were exploited to unravel cross-correlations between features that are hidden in the linear regression analysis. Although the LAL-generated Cu nanocrystals may be present in a range of oxidation states, from metallic copper to cuprous oxide (Cu2O) and cupric oxide (CuO), in addition to the formation of other materials such as Cu2S and CuCN, ML was able to guide the experiments toward the maximization of the compounds in the greatest demand for integration in sustainable processes. This approach is of general applicability to other nanomaterials and can help understand the origin of the chemical pathways of nanocrystals generated by LAL, providing a rational guideline for the conscious predetermination of laser-synthesis parameters toward the desired compounds.

Structural evolution under physical and chemical stimuli of metastable Au-Fe nanoalloys obtained by laser ablation in liquid.

Metastable alloy nanoparticles are investigated for their variety of appealing properties exploitable for photonics, magnetism, catalysis and nanobiotechnology. Notably, nanophases out of thermodynamic equilibrium feature a complex "ultrastructure" leading to a dynamic evolution of composition and atomic arrangement in response to physical-chemical stimuli. In this manuscript, metastable Au-Fe alloy nanoparticles were produced by laser ablation in liquid, an emerging versatile synthetic approach for freezing multielement nanosystems in non-equilibrium conditions. The Au-Fe nanoalloys were characterized through electron microscopy, elemental analysis, X-ray diffraction and Mössbauer spectroscopy. The dynamics of the structure of the Au-Fe system was tracked at high temperature under vacuum and atmospheric conditions, evidencing the intrinsic transformative nature of the metastable nanoalloy produced by laser ablation in liquid. This dynamic structure is relevant to possible application in several fields, from photocatalysis to nanomedicine, as demonstrated through an experiment of magnetic resonance imaging in biological fluids.

Anticancer and Targeting Activity of Phytopharmaceutical Structural Analogs of a Natural Peptide from Trichoderma longibrachiatum and Related Peptide-Decorated Gold Nanoparticles.

In the large field of bioactive peptides, peptaibols represent a unique class of compounds. They are membrane-active peptides, produced by fungi of the genus Trichoderma and known to elicit plant defenses. Among the short-length peptaibols, trichogin GA IV is nonhemolytic, proteolysis-resistant, antibacterial, and cytotoxic. Several trichogin analogs are endowed with potent activity against phytopathogens, thus representing a sustainable alternative to copper for plant protection. In this work, we tested the activity of trichogin analogs against a breast cancer cell line and a normal cell line of the same derivation. Lys-containing trichogins showed an IC50 below 12 µM, a peptide concentration not significantly affecting the viability of normal cells. Two analogs were found to be membrane-active but noncytotoxic. They were anchored to gold nanoparticles (GNPs) and further investigated for their ability to act as targeting agents. GNP uptake by cancer cells increased with peptide decoration, while it decreased in the corresponding normal epithelial cells. This work highlights the promising biological properties of peptaibol analogs in the field of cancer therapy either as cytotoxic molecules or as active targeting agents in drug delivery.

Recent Developments in Plasmonic Alloy Nanoparticles: Synthesis, Modelling, Properties and Applications.

Despite the traditional plasmonic materials are counted on one hand, there are a lot of possible combinations leading to alloys with other elements of the periodic table, in particular those renowned for magnetic or catalytic properties. It is not a surprise, therefore, that nanoalloys are considered for their ability to open new perspectives in the panorama of plasmonics, representing a leading research sector nowadays. This is demonstrated by a long list of studies describing multiple applications of nanoalloys in photonics, photocatalysis, sensing and magneto-optics, where plasmons are combined with other physical and chemical phenomena. In some remarkable cases, the amplification of the conventional properties and even new effects emerged. However, this field is still in its infancy and several challenges must be overcome, starting with the synthesis (control of composition, crystalline order, size, processability, achievement of metastable phases and disordered compounds) as well as the modelling of the structure and properties (accuracy of results, reliability of structural predictions, description of disordered phases, evolution over time) of nanoalloys. To foster the research on plasmonic nanoalloys, here we provide an overview of the most recent results and developments in the field, organized according to synthetic strategies, modelling approaches, dominant properties and reported applications. Considering the several plasmonic nanoalloys under development as well as the large number of those still awaiting synthesis, modelling, properties assessment and technological exploitation, we expect a great impact on the forthcoming solutions for sustainability, ultrasensitive and accurate detection, information processing and many other fields.

Laser-Assisted Synthesis of Non-Equilibrium Nanoalloys.

Vincenzo Amendola is Professor of Physical Chemistry at Padova University, where he established and directs the Laser-Assisted Synthesis and Plasmonics (LASP) lab. He obtained a PhD in Materials Science and Engineering in 2008 and the Italian qualification as Full Professor in 2017, after research experience at Massachusetts Institute of Technology and Cambridge University. He is part of the Program Committee of the ANGEL conference series and he is a current member of the ChemPhysChem Editorial Advisory Board.

Kinetically Stable Nonequilibrium Gold-Cobalt Alloy Nanoparticles with Magnetic and Plasmonic Properties Obtained by Laser Ablation in Liquid.

Nonequilibrium nanoalloys are metastable solids obtained at the nanoscale under nonequilibrium conditions that allow the study of kinetically frozen atoms and the discovery of new physical and chemical properties. However, the stabilization of metastable phases in the nanometric size regime is challenging and the synthetic route should be easy and sustainable, for the nonequilibrium nanoalloys to be practically available. Here we report on the one-step laser ablation synthesis in solution (LASiS) of nonequilibrium Au-Co alloy nanoparticles (NPs) and their characterization on ensembles and at the single nanoparticle level. The NPs are obtained as a polycrystalline solid solution stable in air and water, although surface cobalt atoms undergo oxidation to Co(II). Since gold is a renowned plasmonic material and metallic cobalt is ferromagnetic at room temperature, these properties are both found in the NPs. Besides, surface conjugation with thiolated molecules is possible and it was exploited to obtain colloidally stable solutions in water. Taking advantage of these features, an array of magnetic-plasmonic dots was obtained and used for surface-enhanced Raman scattering experiments. Overall, this study confirms that LASiS is an effective method for the formation of kinetically stable nonequilibrium nanoalloys and shows that Au-Co alloy NPs are appealing magnetically responsive plasmonic building blocks for several nanotechnological applications.

Room-Temperature Laser Synthesis in Liquid of Oxide, Metal-Oxide Core-Shells, and Doped Oxide Nanoparticles.

Although oxide nanoparticles are ubiquitous in science and technology, a multitude of compositions, phases, structures, and doping levels exist, each one requiring a variety of conditions for their synthesis and modification. Besides, experimental procedures are frequently dominated by high temperatures or pressures and by chemical contaminants or waste. In recent years, laser synthesis of colloids emerged as a versatile approach to access a library of clean oxide nanoparticles relying on only four main strategies running at room temperature and ambient pressure: laser ablation in liquid, laser fragmentation in liquid, laser melting in liquid and laser defect-engineering in liquid. Here, established laser-based methodologies are reviewed through the presentation of a panorama of oxide nanoparticles which include pure oxidic phases, as well as unconventional structures like defective or doped oxides, non-equilibrium compounds, metal-oxide core-shells and other anisotropic morphologies. So far, these materials showed several useful properties that are discussed with special emphasis on catalytic, biomedical and optical application. Yet, given the endless number of mixed compounds accessible by the laser-assisted methodologies, there is still a lot of room to expand the library of nano-crystals and to refine the control over products as well as to improve the understanding of the whole process of nanoparticle formation. To that end, this review aims to identify the perspectives and unique opportunities of laser-based synthesis and processing of colloids for future studies of oxide nanomaterial-oriented sciences.

Electronic Structure-Dependent Surface Plasmon Resonance in Single Au-Fe Nanoalloys.

The relationship between composition and plasmonic properties in noble metal nanoalloys is still largely unexplored. Yet, nanoalloys of noble metals, such as gold, with transition elements, such as iron, have unique properties and a number of potential applications, ranging from nanomedicine to magneto-plasmonics and plasmon-enhanced catalysis. Here, we investigate the localized surface plasmon resonance at the level of the single Au-Fe nanoparticle by applying a strategy that combines experimental measurements using near field electron energy loss spectroscopy with theoretical studies via a full wave numerical analysis and density functional theory calculations of electronic structure. We show that, as the iron fraction increases, the plasmon resonance is blue-shifted and significantly damped, as a consequence of the changes in the electronic band structure of the alloy. This allows the identification of three relevant phenomena to be considered in the design and realization of any plasmonic nanoalloy, specifically: the appearance of new states around the Fermi level; the change in the free electron density of the metal; and the blue shift of interband transitions. Overall, this study provides new opportunities for the control of the optical response in Au-Fe and other plasmonic nanoalloys, which are useful for the realization of magneto-plasmonic devices for molecular sensing, thermo-plasmonics, bioimaging, photocatalysis, and the amplification of spectroscopic signals by local field enhancement.

Magnetically Assembled SERS Substrates Composed of Iron-Silver Nanoparticles Obtained by Laser Ablation in Liquid.

The widespread application of surface-enhanced Raman scattering (SERS) would benefit from simple and scalable self-assembly procedures for the realization of plasmonic arrays with a high density of electromagnetic hot-spots. To this aim, the exploitation of iron-doped silver nanoparticles (NPs) synthesized by laser ablation of a bulk bimetallic iron-silver target immersed in ethanol is described. The use of laser ablation in liquid is key to achieving bimetallic NPs in one step with a clean surface available for functionalization with the desired thiolated molecules. These iron-silver NPs show SERS performances, a ready response to external magnetic fields and complete flexibility in surface coating. All these characteristics were used for the magnetic assembly of plasmonic arrays which served as SERS substrates for the identification of molecules of analytical interest. The magnetic assembly of NPs allowed a 28-fold increase in the SERS signal of analytes compared to not-assembled NPs. The versatility of substrate preparation and the SERS performances were investigated as a function of NPs surface coating among different thiolated ligands. These results show a simple procedure to obtain magnetically assembled regenerable plasmonic arrays for repeated SERS investigation of different samples, and it can be of inspiration for the realization of other self-assembled and reconfigurable magnetic-plasmonic devices.

High-Purity Hybrid Organolead Halide Perovskite Nanoparticles Obtained by Pulsed-Laser Irradiation in Liquid.

Nanoparticles of hybrid organic-inorganic perovskites have attracted a great deal of attention due to their variety of optoelectronic properties, their low cost, and their easier integration into devices with complex geometry, compared with microcrystalline, thin-film, or bulk metal halides. Here we present a novel one-step synthesis of organolead bromide perovskite nanocrystals based on pulsed-laser irradiation in a liquid environment (PLIL). Starting from a bulk CH3 NH3 PbBr3 crystal, our PLIL procedure does not involve the use of high-boiling-point polar solvents or templating agents, and runs at room temperature. The resulting nanoparticles are characterized by high crystallinity and are completely free of any microscopic product or organic coating layer. We also demonstrate the straightforward inclusion of laser-generated perovskite nanocrystals in a polymeric matrix to form a nanocomposite with single- and two-photon luminescence properties.

Enhanced Electrocatalytic Oxygen Evolution in Au-Fe Nanoalloys.

Oxygen evolution reaction (OER) is the most critical step in water splitting, still limiting the development of efficient alkaline water electrolyzers. Here we investigate the OER activity of Au-Fe nanoalloys obtained by laser-ablation synthesis in solution. This method allows a high amount of iron (up to 11 at %) to be incorporated into the gold lattice, which is not possible in Au-Fe alloys synthesized by other routes, due to thermodynamic constraints. The Au0.89 Fe0.11 nanoalloys exhibit strongly enhanced OER in comparison to the individual pure metal nanoparticles, lowering the onset of OER and increasing up to 20 times the current density in alkaline aqueous solutions. Such a remarkable electrocatalytic activity is associated to nanoalloying, as demonstrated by comparative examples with physical mixtures of gold and iron nanoparticles. These results open attractive scenarios to the use of kinetically stable nanoalloys for catalysis and energy conversion.

Detection of low-quantity anticancer drugs by surface-enhanced Raman scattering.

Ultrasensitive detection of low-quantity drugs is important for personalized therapeutic approaches in several diseases and, in particular, for cancer treatment. In this field, surface-enhanced Raman scattering (SERS) can be very useful for its ability to precisely identify analytes from their unique vibrational spectra, with very high sensitivity. Here, we report a study about SERS detection of sunitinib, paclitaxel and irinotecan, i.e. three commonly used antineoplastic drugs, and of SN-38, i.e. the metabolite of irinotecan, dissolved in methanol solutions. By using commercial Klarite substrates, we found that sunitinib, irinotecan and SN-38 have detection limits of 20-70 ng, which is below the threshold for applications in cancer therapy. Conversely, the SERS signal was not appreciable with paclitaxel, and this is explained by the absence of optical resonances in the visible range. Overall, our results show that ultrasensitive SERS detection of sunitinib, irinotecan and SN-38 is feasible, encouraging further development of this technology also for other drugs with similar molecular structure especially for those analytes with absorption bands in the visible range.

Surface plasmon resonance of silver and gold nanoparticles in the proximity of graphene studied using the discrete dipole approximation method.

The integration of silver and gold nanoparticles with graphene is frequently sought for the realization of hybrid materials with superior optical, photoelectric and photocatalytic performances. A crucial aspect for these applications is how the surface plasmon resonance of metal nanoparticles is modified after assembly with graphene. Here, we used the discrete dipole approximation method to study the surface plasmon resonance of silver and gold nanoparticles in the proximity of a graphene flake or embedded in graphene structures. Surface plasmon resonance modifications were investigated for various shapes of metal nanoparticles and for different morphologies of the nanoparticle-graphene nanohybrids, in a step-by-step approach. Calculations show that the surface plasmon resonance of Ag nanoparticles is quenched in nanohybrids, whereas either surface plasmon quenching or enhancement can be obtained with Au nanoparticles, depending on the configuration adopted. However, graphene effects on the surface plasmon resonance are rapidly lost already at a distance of the order of 5 nm. These results provide useful indications for characterization and monitoring the synthesis of hybrid nanostructures, as well as for the development of hybrid metal nanoparticle/graphene nanomaterials with desired optical properties.

Metastable alloy nanoparticles, metal-oxide nanocrescents and nanoshells generated by laser ablation in liquid solution: influence of the chemical environment on structure and composition.

Alloy nanoparticles are characterized by the combination of multiple interesting properties, which are attractive for technological and scientific purposes. A frontier topic of this field is nanoalloys with compositions not thermodynamically allowed at ordinary temperature and pressure (i.e. metastable), because they require out-of-equilibrium synthetic approaches. Recently, laser ablation synthesis in solution (LASiS) was successfully applied for the realization of metastable nanoalloys because of the fast kinetics of nanoparticle formation. However, the role played by the chemical environment on the final composition and structure of laser generated nanoalloys still has to be fully elucidated. Here, we investigated the influence of different synthetic conditions on the LASiS of metastable nanoalloys composed of Au and Fe, such as the use of water instead of ethanol, the bubbling of inert gases and the addition of a few vol% of H2O2 and H2O. The two elements showed different reactivity when LASiS was performed in water instead of ethanol, while minor effects were observed from bubbling pure gases such as N2, Ar and CO2 in the liquid solution. Moreover, the plasmonic response and the structure of the nanoalloys were sensibly modified by adding H2O2 to water. We also found that nanoparticle production is dramatically influenced just by adding 0.2% of H2O in ethanol. These results suggest that the formation of a cavitation bubble with long lifetime and large size during LASiS is useful for the preservation of the metastable alloy composition, whereas an oxidative environment hampers the formation of metastable alloy nanoparticles. Overall, by acting on the type of solvent and solutes, we were able to switch from a traditional synthetic approach for the composition of Au-Fe nanoalloys to one using a reactive environment, which gives unconventional structures such as metal@iron-oxide nanoshells and nanocrescents of oxide supported on metal nanospheres. These results expand the knowledge about the mechanism of the formation of nanoalloys using LASiS and show how to obtain multielement nanoparticles of enormous interest for nanomedicine, plasmonics, magneto-plasmonics and catalysis.

A General Technique to Investigate the Aggregation of Nanoparticles by Transmission Electron Microscopy.

The aggregation state of nanoparticles (NPs) must be precisely known in order to study the structure-property relationship and to evaluate the exploitability of NPs dispersion for a given application. Here we report a general technique for sample preparation to investigate with transmission electron microscopy (TEM) the state of aggregation of NPs dispersed in liquid solution. Following a simple procedure which requires few minutes, the aggregates of NPs are "frozen" in a polymeric matrix simultaneously to their deposition on a TEM grid. Our technique is of general applicability and it avoids the use of cryo-TEM, which is more expensive, more time consuming and less common than ordinary TEM. Compared to the investigation of NPs aggregation in the liquid phase with dynamic light scattering, our approach avoids the problem of shielding by large aggregates and it allows the full exploitation of TEM advantages, primarily the reliable determination of shape and size of each aggregate and the precise evaluation of the number of single NPs forming each cluster. As an example, we demonstrate the use of our technique to study two frequent topics related to aggregation: the plasmon properties of gold NPs aggregates and the stability of iron oxide NPs in physiological environment. The methodology described here will be useful to advance the knowledge about how aggregation influences the physical-chemical properties of NPs.

Magneto-plasmonic Au-Fe alloy nanoparticles designed for multimodal SERS-MRI-CT imaging.

Diagnostic approaches based on multimodal imaging are needed for accurate selection of the therapeutic regimens in several diseases, although the dose of administered contrast drugs must be reduced to minimize side effects. Therefore, large efforts are deployed in the development of multimodal contrast agents (MCAs) that permit the complementary visualization of the same diseased area with different sensitivity and different spatial resolution by applying multiple diagnostic techniques. Ideally, MCAs should also allow imaging of diseased tissues with high spatial resolution during surgical interventions. Here a new system based on multifunctional Au-Fe alloy nanoparticles designed to satisfy the main requirements of an ideal MCA is reported and their biocompatibility and imaging capability are described. The MCAs show easy and versatile surface conjugation with thiolated molecules, magnetic resonance imaging (MRI) and computed X-ray tomography (CT) signals for anatomical and physiological information (i.e., diagnostic and prognostic imaging), large Raman signals amplified by surface enhanced Raman scattering (SERS) for high sensitivity and high resolution intrasurgical imaging, biocompatibility, exploitability for in vivo use and capability of selective accumulation in tumors by enhanced permeability and retention effect. Taken together, these results show that Au-Fe nanoalloys are excellent candidates as multimodal MRI-CT-SERS imaging agents.