Injectable Thermogelling Nanostructured Ink as Simultaneous Optical and Magnetic Resonance Imaging Contrast Agent for Image-Guided Surgery.

The development of efficient and biocompatible contrast agents is particularly urgent for modern clinical surgery. Nanostructured materials raised great interest as contrast agents for different imaging techniques, for which essential features are high contrasts, and in the case of precise clinical surgery, minimization of the signal spatial dispersion when embedded in biological tissues. This study deals with the development of a multimodal contrast agent based on an injectable hydrogel nanocomposite containing a lanthanide-activated layered double hydroxide coupled to a biocompatible dye (indocyanine green), emitting in the first biological window. This novel nanostructured thermogelling hydrogel behaves as an efficient tissue marker for optical and magnetic resonance imaging because the particular formulation strongly limits its spatial diffusion in biological tissue by exploiting a simple injection. The synergistic combination of these properties permits to employ the hydrogel ink simultaneously for both optical and magnetic resonance imaging, easy monitoring of the biological target, and, at the same time, increasing the spatial resolution during a clinical surgery. The biocompatibility and excellent performance as contrast agents are very promising for possible use in image-guided surgery, which is currently one of the most challenging topics in clinical research.

Exploring the Phase-Selective, Green, Hydrothermal Synthesis of Upconverting Doped Sodium Yttrium Fluoride: Effects of Temperature, Time, and Precursors.

The aim of this work was i) to develop a hydrothermal, low-temperature synthesis protocol affording the upconverting hexagonal phase NaYF4 with suitable dopants while adhering to the "green chemistry" standards and ii) to explore the effect that different parameters have on the products. In optimizing the synthesis protocol, short reaction times and low temperatures (below 150 °C) were considered. Yb3+ and Er3+ ions were chosen as dopants for the NaYF4 material. Within the context of the second goal, parameters including nature of the precursors, treatment temperature, and treatment time were investigated to afford a pure hexagonal crystalline phase, both in the doped and undoped materials. To fully explore the synthesis results, the prepared materials were characterized from a structural (XRD), compositional (XPS, ICP-MS), and morphological (SEM) point of view. The upconverting properties of the compounds were confirmed by photoluminescence measurements.

Novel sol-gel fabrication of Yb3+/Tm3+ co-doped ß-NaYF4 thin films and investigation of their upconversion properties.

An innovative sol-gel process, using a mixture of Na(hfa)·tetraglyme and RE(hfa)3·diglyme (RE = Y, Yb, Tm) complexes, has been optimized to produce upconverting ß-NaYF4:Yb3+/Tm3+ thin films. The X-ray diffraction (XRD) analysis confirms that the new sol-gel preparation route yields reproducibly and selectively the hexagonal Na(Y1.5Na0.5)F6 structure (ß-NaYF4) without any impurity phases, since no peaks of the cubic NaYF4, YOF, Y2O3 or NaF phases were observed. This final goal has been achieved through an accurate optimization of the operative parameters such as the molar ratio of the precursor mixture, the aging time of the sol, the spin coating procedure and the annealing temperature. Field-emission scanning electron microscopy (FE-SEM) images indicate that the morphology of the surfaces, grain dimensions and thickness are strongly related to the processing parameters, with the hexagonal phase films having a very uniform morphology. Energy dispersive X-ray (EDX) analyses established the film composition in terms of dopant ions, which are responsible for the upconverting properties of the material. Luminescence measurements under laser excitation at 980 nm confirmed the promising upconversion properties of the ß-NaYF4:Yb3+/Tm3+ films.

Paramagnetic Nanoparticles Leave Their Mark on Nuclear Spins of Transiently Adsorbed Proteins.

The successful application of nanomaterials in biosciences necessitates an in-depth understanding of how they interface with biomolecules. Transient associations of proteins with nanoparticles (NPs) are accessible by solution NMR spectroscopy, albeit with some limitations. The incorporation of paramagnetic centers into NPs offers new opportunities to explore bio-nano interfaces. We propose NMR paramagnetic relaxation enhancement as a new tool to detect NP-binding surfaces on proteins with increased sensitivity, also extending the applicability of NMR investigations to heterogeneous biomolecular mixtures. The adsorption of ubiquitin on gadolinium-doped fluoride-based NPs produced residue-specific NMR line-broadening effects mapping to a contiguous area on the surface of the protein. Importantly, an identical paramagnetic fingerprint was observed in the presence of a competing protein-protein association equilibrium, exemplifying possible interactions taking place in crowded biological media. The interaction was further characterized using isothermal titration calorimetry and upconversion emission measurements. The data indicate that the used fluoride-based NPs are not biologically inert but rather are capable of biomolecular recognition.

Enhancing optical forces on fluorescent up-converting nanoparticles by surface charge tailoring.

3D remote control of multifunctional fluorescent up-converting nanoparticles (UCNPs) using optical forces is being required for a great variety of applications including single-particle spectroscopy, single-particle intracellular sensing, controlled and selective light-activated drug delivery and light control at the nanoscale. Most of these potential applications find a serious limitation in the reduced value of optical forces (tens of fN) acting on these nanoparticles, due to their reduced dimensions (typically around 10 nm). In this work, this limitation is faced and it is demonstrated that the magnitude of optical forces acting on UCNPs can be enhanced by more than one order of magnitude by a controlled modification of the particle/medium interface. In particular, substitution of cationic species at the surface by other species with higher mobility could lead to UCNPs trapping with constants comparable to those of spherical metallic nanoparticles.

Fabrication of Europium-Doped CaF2 Films via Sol-Gel Synthesis as Down-Shifting Layers for Solar Cell Applications.

In the present work, an in-depth study on the sol-gel process for the fabrication of Eu-doped CaF2 materials in the form of thin films has been addressed for the production of down-shifting layers. Fine-tuning of the operative parameters, such as the annealing temperature, substrate nature and doping ion percentage, has been finalized in order to obtain Eu(III)-doped CaF2 thin films via a reproducible and selective solution process for down-shifting applications. An accurate balance of such parameters allows for obtaining films with high uniformity in terms of both their structural and compositional features. The starting point of the synthesis is the use of a mixture of Ca(hfa)2•diglyme•H2O and Eu(hfa)3•diglyme adducts, with a suited ratio to produce 5%, 10% and 15% Eu-doped CaF2 films, in a water/ethanol solution. A full investigation of the structural, morphological and compositional features of the films, inspected using X-ray diffraction analysis (XRD), field emission scanning electron microscopy (FE-SEM) and energy dispersive X-ray analysis (EDX), respectively, has stated a correlation between the annealing temperature and the structural characteristics and morphology of the CaF2 thin films. Interestingly, crystalline CaF2 films are obtained at quite low temperatures of 350-400 °C. The down-shifting properties, validated by taking luminescence measurements under UV excitation, have allowed us to correlate the local environment in terms of the degree of symmetry around the europium ions with the relative doping ion percentages.

Chirality in luminescent Cs3Cu2Br5 microcrystals produced via ligand-assisted reprecipitation.

Herein we report new chiral luminescent Cs3Cu2Br5 needle-like microcrystals and the analysis of their optical properties and the effect of the ligand structure on the transfer of chirality.

From Nanothermometry to Bioimaging: Lanthanide-Activated KY3F10 Nanostructures as Biocompatible Multifunctional Tools for Nanomedicine.

Lanthanide-activated fluoride-based nanostructures are extremely interesting multifunctional tools for many modern applications in nanomedicine, e.g., bioimaging, sensing, drug delivery, and photodynamic therapy. Importantly, environmental-friendly preparations using a green chemistry approach, as hydrothermal synthesis route, are nowadays highly desirable to obtain colloidal nanoparticles, directly dispersible in hydrophilic media, as physiological solution. The nanomaterials under investigation are new KY3F10-based citrate-capped core@shell nanostructures activated with several lanthanide ions, namely, Er3+, Yb3+, Nd3+, and Gd3+, prepared as colloidal water dispersions. A new facile microwave-assisted synthesis has been exploited for their preparation, with significant reduction of the reaction times and a fine control of the nanoparticle size. These core@shell multifunctional architectures have been investigated for use as biocompatible and efficient contrast agents for optical, magnetic resonance imaging (MRI) and computerized tomography (CT) techniques. These multifunctional nanostructures are also efficient noninvasive optical nanothermometers. In fact, the lanthanide emission intensities have shown a relevant relative variation as a function of the temperature, in the visible and near-infrared optical ranges, efficiently exploiting ratiometric intensity methods for optical thermometry. Importantly, in contrast with other fluoride hosts, chemical dissolution of KY3F10 citrate-capped nanocrystals in aqueous environment is very limited, of paramount importance for applications in biological fluids. Furthermore, due to the strong paramagnetic properties of lanthanides (e.g., Gd3+), and X-ray absorption of both yttrium and lanthanides, the nanostructures under investigation are extremely useful for MRI and CT imaging. Biocompatibility studies of the nanomaterials have revealed very low cytotoxicity in dfferent human cell lines. All these features point to a successful use of these fluoride-based core@shell nanoarchitectures for simultaneous diagnostics and temperature sensing, ensuring an excellent biocompatibility.

Chiral non-stoichiometric ternary silver indium sulfide quantum dots: investigation on the chirality transfer by cysteine.

Chiral semiconductor quantum dots have recently received broad attention due to their promising application in several fields such as sensing and photonics. The extensive work in the last few years was focused on the observation of the chiroptical properties in binary Cd based systems. Herein, we report on the first evidence of ligand-induced chirality in silver indium sulfide semiconductor quantum dots. Ternary disulfide quantum dots are of great interest due to their remarkable optical properties and low toxicity. Non-stoichiometric silver indium sulfide quantum dots were produced via a room temperature coprecipitation in water, in the presence of cysteine as a capping agent. The obtained nanocrystals show a notable photoluminescence quantum yield of 0.24 in water dispersions. Several critical aspects of the nanocrystal growth and chemico-physical characterization, and the optimisation of the surface passivation by the chiral ligand in order to optimize the nanoparticle chirality are thoroughly investigated. Optical spectroscopy methods such as circular dichroism and luminescence as well as nuclear magnetic resonance techniques are exploited to analyze the coordination processes leading to the formation of the ligand-nanocrystal chiral interface. This study highlights the dynamic nature of the interaction between the nanocrystal surface and the chiral ligand and clarifies some fundamental aspects for the transfer and optimization of the chiroptical properties.

Synthesis, characterization and photocatalytic properties of nanostructured lanthanide doped ß-NaYF4/TiO2 composite films.

The photocatalytic approach is known to be one of the most promising advanced oxidation processes for the tertiary treatment of polluted water. In this paper, ß-NaYF4/TiO2 composite films have been synthetized through a novel sol-gel/spin-coating approach using a mixture of ß-diketonate complexes of Na and Y, and Yb3+, Tm3+, Gd3+, Eu3+ as doping ions, together with the TiO2 P25 nanoparticles. The herein pioneering approach represents an easy, straightforward and industrially appealing method for the fabrication of doped ß-NaYF4/TiO2 composites. The effect of the doped ß-NaYF4 phase on the photocatalytic activity of TiO2 for the degradation of methylene blue (MB) has been deeply investigated. In particular, the upconverting TiO2/ß-NaYF4: 20%Yb, 2% Gd, x% Tm (x = 0.5 and 1%) and the downshifting TiO2/ß-NaYF4: 10% Eu composite films have been tested on MB degradation both under UV and visible light irradiation. An improvement up to 42.4% in the degradation of MB has been observed for the TiO2/ß-NaYF4: 10% Eu system after 240 min of UV irradiation.

Cubic versus hexagonal - phase, size and morphology effects on the photoluminescence quantum yield of NaGdF4:Er3+/Yb3+ upconverting nanoparticles.

Upconverting nanoparticles (UCNPs) are well-known for their capacity to convert near-infrared light into UV/visible light, benefitting various applications where light triggering is required. At the nanoscale, loss of luminescence intensity is observed and thus, a decrease in photoluminescence quantum yield (PLQY), usually ascribed to surface quenching. We evaluate this by measuring the PLQY of NaGdF4:Er3+,Yb3+ UCNPs as a function of size (ca. 15 to 100 nm) and shape (spheres, cubes, hexagons). Our results show that the PLQY of α-phase NaGdF4 Er3+,Yb3+ surpasses that of ß-NaGdF4 for sizes below 20 nm, an observation related to distortion of the crystal lattice when the UCNPs become smaller. The present study also underlines that particle shape must not be neglected as a relevant parameter for PLQY. In fact, based on a mathematical nucleus/hull volumetric model, shape was found to be particularly relevant in the 20 to 60 nm size range of the investigated UCNPs.

Doped Ferrite Nanoparticles Exhibiting Self-Regulating Temperature as Magnetic Fluid Hyperthermia Antitumoral Agents, with Diagnostic Capability in Magnetic Resonance Imaging and Magnetic Particle Imaging.

This paper reports a comprehensive investigation of a magnetic nanoparticle (MNP), named M55, which belongs to a class of innovative doped ferrite nanomaterials, characterized by a self-limiting temperature. M55 is obtained from M48, an MNP previously described by our group, by implementing an additional purification step in the synthesis. M55, after citrate and glucose coating, is named G-M55. The present study aimed to demonstrate the properties of G-M55 as a diagnostic contrast agent for MRI and magnetic particle imaging (MPI), and as an antitumoral agent in magnetic fluid hyperthermia (MFH). Similar specific absorption rate values were obtained by standard MFH and by an MPI apparatus. This result is of interest in relation to the application of localized MFH by MPI apparatus. We demonstrated the biocompatibility of G-M55 in a triple-negative human breast cancer line (MDA-MB-231), and its efficacy as an MFH agent in the same cell line. We also demonstrated the efficacy of MFH treatment with G-M55 in an experimental model of breast cancer. Overall, our results pave the way for the clinical application of G-M55 as an MFH agent in breast cancer therapy, allowing not only efficient treatment by both standard MFH apparatus and MPI but also temperature monitoring.

The formation mechanism and chirality evolution of chiral carbon dots prepared via radical assisted synthesis at room temperature.

We report on a Cu(ii) catalyzed process for the production of cysteine based chiral carbon dots; the process does not require any thermal treatment and the carbon dot formation is driven by the production of reactive radical species that are generated in the reaction media by the catalytic role played by the multivalent transition metal. The nanomaterial presents a well-defined chirality and the enantioselectivity of the synthesis is proved by the isolation of both the carbon dot enantiomers. We focused our attention on the processes that take place during the carbon dot formation and the relationship with the structure of the organic starting material. Thanks to the comparison of reactions conducted with different organic substrates whose thiyl radical chemistry is known, we recognized a non-trivial role of the radical hydrogen abstraction reactions in the carbon dot formation process. The reported process allows access to a large variety of analyses to monitor the reaction mixtures during the reaction course. Finally, we report a detailed analysis on the evolution of optical chirality during the synthesis and related this feature with the formation mechanism of the nanomaterial revealing significant evidence on the chirality origin and structure of chiral carbon dots.

Nanoparticles exhibiting self-regulating temperature as innovative agents for Magnetic Fluid Hyperthermia.

During the last few years, for therapeutic purposes in oncology, considerable attention has been focused on a method called magnetic fluid hyperthermia (MFH) based on local heating of tumor cells. In this paper, an innovative, promising nanomaterial, M48 composed of iron oxide-based phases has been tested. M48 shows self-regulating temperature due to the observable second order magnetic phase transition from ferromagnetic to paramagnetic state. A specific hydrophilic coating based on both citrate ions and glucose molecules allows high biocompatibility of the nanomaterial in biological matrices and its use in vivo. MFH mediator efficiency is demonstrated in vitro and in vivo in breast cancer cells and tumors, confirming excellent features for biomedical application. The temperature increase, up to the Curie temperature, gives rise to a phase transition from ferromagnetic to paramagnetic state, promoting a shortage of the r2 transversal relaxivity that allows a switch in the contrast in Magnetic Resonance Imaging (MRI). Combining this feature with a competitive high transversal (spin-spin) relaxivity, M48 paves the way for a new class of temperature sensitive T2 relaxing contrast agents. Overall, the results obtained in this study prepare for a more affordable and tunable heating mechanism preventing the damages of the surrounding healthy tissues and, at the same time, allowing monitoring of the temperature reached.

Eu-doped titania nanofibers: processing, thermal behaviour and luminescent properties.

Undoped and Europium-doped titania nanofibers have been fabricated by electrospinning technique, using a single multielement Titanium/Europium source. In this communication we present the synthesis, structural and spectroscopic characterisation of Eu-doped TiO2 nanofibers starting from polyvinylpyrrolidone, titanium tetraisopropoxide (Ti(OiPr)4) and Eu(hfa)3 x diglyme (Hhfa = 1,1,1,5,5,5-hexafluoroacetyacetone, diglyme = CH3O(CH2CH2O)2CH3). The chosen system allowed to investigate a wide compositional range, i.e., from 3 to 10% mol of Eu3+. Microstructure was studied by means of scanning electron microscopy (SEM), thermal behaviour followed by thermogravimetric and differential thermal analysis (TG-DTA). Phase analysis was performed by means of X-ray diffraction (XRD) and high temperature X-ray diffraction analysis (HT-XRD) up to 1100 degrees C. Luminescence properties were investigated by means of luminescence spectroscopy, using a laser excitation source at 395 nm. All electrospun materials consisted of randomly oriented nanofibers of fairly uniform diameter. The average fiber size was 80-100 nm and 40 nm for, respectively, Eu-doped and undoped TiO2 calcinated at 500 degrees C. The presence of Europium shifted toward higher values either the crystallization temperature of anatase and the anatase to rutile phase transition, the latter being accompanied by the formation of the Eu2Ti2O7 phase. The doped samples showed a strong luminescence of Eu3+ ions. The emission spectra were dominated by the 5D0 --> 7F2 emission, suggesting a notable distortion around the Eu3+ ions. The broadening of the bands pointed to the presence of a relevant inhomogeneous disorder around the Eu3+ sites. The Eu3+ doped TiO2 nanofibers showed a higher emission intensity with respect to the PVP/TiO2 ones.

Sodium niobate based hierarchical 3D perovskite nanoparticle clusters.

We report a microwave assisted synthesis of NaNbO3 perovskite mesocrystals with a hierarchical morphology formed by the self-assembly of nanoparticles in particle clusters. The synthesis method combines non-aqueous sol-gel synthesis and microwave heating in a single step process that allows us to isolate crystalline single phase NaNbO3 in few minutes. A detailed investigation of the effect of the reaction temperature on the crystallinity and morphology of the product was conducted. The synthesis stabilizes the unusual orthorhombic phase Pmma, a property that can be ascribed to the crystal size (24 nm). TEM and SAED analyses show that the hierarchical polycrystalline particles behave as single crystals, a feature related to a non-classical crystallization mechanism. Moreover, the optical bandgap of this NaNbO3 phase was estimated for the first time. The results suggest the potential of this synthetic procedure for the fast production of high quality tertiary oxide nanocrystals.

Microfluidic Crystallization of Surfactant-Free Doped Zinc Sulfide Nanoparticles for Optical Bioimaging Applications.

The room-temperature controlled crystallization of monodispersed ZnS nanoparticles (average size of 5 nm) doped with luminescent ions (such as Mn2+, Eu3+, Sm3+, Nd3+, and Yb3+) was achieved via a microfluidic approach. The preparation did not require any stabilizing ligands or surfactants, minimizing potential sources of impurities. The synthesized nanomaterials were characterized from a structural (XRD and XAS at lanthanide L3 edges), morphological (TEM), and compositional (XPS, ICP-MS) perspective, giving complementary information on the materials' features. In view of potential applications in the field of optical bioimaging, the optical emission properties of the doped nanoparticles were assessed, and samples showed strong luminescent properties while being less affected by self-quenching mechanisms. Furthermore, in vitro cytotoxicity experiments were conducted, showing no negative effects and evidencing the appeal of the synthesized materials for potential applications in the field of optical bioimaging.

Identification of the structural phases of Ce(x)Zr(1-x)O2 by Eu(III) luminescence studies.

Despite the wide application of ceria-zirconia based materials in Three Way Catalysts (TWCs), Solid Oxides Fuel Cells (SOFCs), and H(2) production and purification reactions, an active debate is still open on the correlation between their structure and redox/catalytic performances. Existing reports support the need of either (i) a homogeneous solid solution or (ii) materials with nanoscale heterogeneity to obtain high activity and stability. Here we report on a simple and inexpensive approach to solve this problem taking advantage of the luminescence properties of Eu(III), used as a structural probe introduced either in the bulk or on the surface of the samples. In this way, the real structure of ceria-zirconia materials can be revealed even for amorphous high surface area samples. Formation of small domains is observed in catalytically important metastable samples which appear homogeneous by conventional XRD.

The f-f emission of Pr3+ ion as an optical probe for the structural properties of YAG nanoceramics.

Transparent Pr-doped YAG nanoceramics composed of grains with an average size of about 42 nm, were fabricated with the Low Temperature High Pressure (LTHP) sintering technique using the corresponding nanopowders as the starting materials. The structure of the nanoceramics was analyzed by X-ray diffraction (XRD). The effect of the sintering conditions on the structural properties is discussed on the basis of the changes of the spectroscopic properties of Pr3+ ions. In particular, the intensities and decays of the emission transitions originating from the (3)P0 and (1)D2 levels are investigated and correlated with structural properties of the material, such as microstrains produced by the high-pressure process.

Engineering efficient upconverting nanothermometers using Eu3+ ions.

Upconversion nanothermometry combines the possibility of optically sensing temperatures in very small areas, such as microfluidic channels or on microelectronic chips, with a simple detection setup in the visible spectral range and reduced heat transfer after near-infrared (NIR) excitation. We propose a ratiometric strategy based on Eu3+ ion luminescence activated through upconversion processes. Yb3+ ions act as a sensitizer in the NIR region (980 nm), and energy is transferred to Tm3+ ions that in turn excite Eu3+ ions whose luminescence is shown to be thermally sensitive. Tridoped SrF2:Yb3+,Tm3+,Eu3+ nanoparticles (average size of 17 nm) show a relative thermal sensitivity of 1.1% K-1 at 25.0 °C, in the range of the best ones reported to date for Ln3+-based nanothermometers based on upconversion emission. The present nanoparticle design allows us to exploit upconversion of lanthanide ions that otherwise cannot be directly excited upon NIR excitation and that may provide operational wavelengths with a highly stable read out to fill the spectral gaps currently existing in upconversion-based nanothermometry.