Magnetoplasmonics beyond Metals: Ultrahigh Sensing Performance in Transparent Conductive Oxide Nanocrystals.

Active modulation of the plasmonic response is at the forefront of today's research in nano-optics. For a fast and reversible modulation, external magnetic fields are among the most promising approaches. However, fundamental limitations of metals hamper the applicability of magnetoplasmonics in real-life active devices. While improved magnetic modulation is achievable using ferromagnetic or ferromagnetic-noble metal hybrid nanostructures, these suffer from severely broadened plasmonic response, ultimately decreasing their performance. Here we propose a paradigm shift in the choice of materials, demonstrating for the first time the outstanding magnetoplasmonic performance of transparent conductive oxide nanocrystals with plasmon resonance in the near-infrared. We report the highest magneto-optical response for a nonmagnetic plasmonic material employing F- and In-codoped CdO nanocrystals, due to the low carrier effective mass and the reduced plasmon line width. The performance of state-of-the-art ferromagnetic nanostructures in magnetoplasmonic refractometric sensing experiments are exceeded, challenging current best-in-class localized plasmon-based approaches.

3d Metal Doping of Core@Shell Wüstite@ferrite Nanoparticles as a Promising Route toward Room Temperature Exchange Bias Magnets.

Nanometric core@shell wüstite@ferrite (Fe1-x O@Fe3 O4 ) has been extensively studied because of the emergence of exchange bias phenomena. Since their actual implementation in modern technologies is hampered by the low temperature at which bias is operating, the critical issue to be solved is to obtain exchange-coupled antiferromagnetic@ferrimagnetic nanoparticles (NPs) with ordering temperature close to 300 K by replacing the divalent iron with other transition-metal ions. Here, the effect of the combined substitution of Fe(II)  with Co(II)  and Ni(II)  on the crystal structure and magnetic properties is studied. To this aim, a series of 20 nm NPs with a wüstite-based core and a ferrite shell, with tailored composition, (Co0.3 Fe0.7 O@Co0.8 Fe2.2 O4  and Ni0.17 Co0.21 Fe0.62 O@Ni0.4 Co0.3 Fe2.3 O4 ) is synthetized through a thermal-decomposition method. An extensive morphological and crystallographic characterization of the obtained NPs shows how a higher stability against the oxidation process in ambient condition is attained when divalent cation doping of the iron oxide lattice with Co(II)  and Ni(II)  ions is performed. The dual-doping is revealed to be an efficient way for tuning the magnetic properties of the final system, obtaining Ni-Co doped iron oxide core@shell NPs with high coercivity (and therefore, high energy product), and increased antiferromagnetic ordering transition temperature, close to room temperature.

Lipid Cubic Mesophases Combined with Superparamagnetic Iron Oxide Nanoparticles: A Hybrid Multifunctional Platform with Tunable Magnetic Properties for Nanomedical Applications.

Hybrid materials composed of superparamagnetic iron oxide nanoparticles (SPIONs) and lipid self-assemblies possess considerable applicative potential in the biomedical field, specifically, for drug/nutrient delivery. Recently, we showed that SPIONs-doped lipid cubic liquid crystals undergo a cubic-to-hexagonal phase transition under the action of temperature or of an alternating magnetic field (AMF). This transition triggers the release of drugs embedded in the lipid scaffold or in the water channels. In this contribution, we address this phenomenon in depth, to fully elucidate the structural details and optimize the design of hybrid multifunctional carriers for drug delivery. Combining small-angle X-ray scattering (SAXS) with a magnetic characterization, we find that, in bulk lipid cubic phases, the cubic-to-hexagonal transition determines the magnetic response of SPIONs. We then extend the investigation from bulk liquid-crystalline phases to colloidal dispersions, i.e., to lipid/SPIONs nanoparticles with cubic internal structure ("magnetocubosomes"). Through Synchrotron SAXS, we monitor the structural response of magnetocubosomes while exposed to an AMF: the magnetic energy, converted into heat by SPIONs, activates the cubic-to-hexagonal transition, and can thus be used as a remote stimulus to spike drug release "on-demand". In addition, we show that the AMF-induced phase transition in magnetocubosomes steers the realignment of SPIONs into linear string assemblies and connect this effect with the change in their magnetic properties, observed at the bulk level. Finally, we assess the internalization ability and cytotoxicity of magnetocubosomes in vitro on HT29 adenocarcinoma cancer cells, in order to test the applicability of these smart carriers in drug delivery applications.

Magnetic Property Enhancement of Spinel Mn-Zn Ferrite through Atomic Structure Control.

Temperature treatment of magnetic Mn-Zn ferrites with the composition Mn0.6Zn0.2Fe2.2O4 up to 1100 °C results in a tremendous enhancement of the saturation magnetization by more than 60%. Employing a robust combined Rietveld refinement of powder X-ray and neutron diffraction (PXRD and NPD) data, it is revealed how a reordering of the cations takes place during the annealing step, the extent of which depends on the annealing temperature. While Zn(II) exclusively occupies tetrahedral sites throughout the whole temperature range, as the annealing temperature increases up to 700 °C, the Mn(II) cation distribution shifts from 80(7)% of the total Mn content occupying the octahedral sites (partly inverse spinel) to Mn only being present on the tetrahedral sites (normal spinel). Above 700 °C, pronounced crystallite growth is observed, followed by an increase of the saturation magnetization. Complementary techniques such as energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM) confirm an even cation distribution and the particle growth with annealing temperature. The structural changes caused by annealing of spinel ferrites directly alter the magnetic properties of the materials, thus serving as an easy handle for enhancing their magnetic properties.

An Approach for Magnetic Halloysite Nanocomposite with Selective Loading of Superparamagnetic Magnetite Nanoparticles in the Lumen.

We present for the first time a method for the preparation of magnetic halloysite nanotubes (HNT) by loading of preformed superparamagnetic magnetite nanoparticles (SPION) of diameter size ∼6 nm with a hydrodynamic diameter of ∼10 nm into HNT. We found that the most effective route to reach this goal relies on the modification of the inner lumen of HNT by tetradecylphosphonic acid (TDP) to give HNT-TDP, followed by the loading with preformed oleic acid (OA)-stabilized SPION. Transmission electron microscopy evidenced the presence of highly crystalline magnetic nanoparticles only in the lumen, partially ordered in chainlike structures. Conversely, attempts to obtain the same result by exploiting either the positive charge of the HNT inner lumen employing SPIONs covered with negatively charged capping agents or the in situ synthesis of SPION by thermal decomposition were not effective. HNT-TDP were characterized by infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), and ζ-potential, and all of the techniques confirmed the presence of TDP onto the HNT. Moreover, the inner localization of TDP was ascertained by the use of Nile Red, a molecule whose luminescence is very sensitive to the polarity of the environment. The free SPION@OA (as a colloidal suspension and as a powder) and SPION-in-HNT powder were magnetically characterized by measuring the ZFC-FC magnetization curves as well as the hysteresis cycles at 300 and 2.5 K, confirming that the super-paramagnetic behavior and the main magnetic properties of the free SPION were preserved once embedded in SPION-in-HNT.

Increasing the Magnetic Anisotropy of a Natural System: Co-Doped Magnetite Mineralized in Ferritin Shells.

Iron oxide nanoparticles mineralized within the internal cavity of Ferritin protein cage are extremely appealing for the realization of multifunctional therapeutic and diagnostic agents for cancer treatment by drug delivery, magnetic fluid hyperthermia (MFH) and magnetic resonance imaging. Being the maximum mean size imposed by the internal diameter of the protein shell (ca. 8 nm) too small for the use of these systems in MFH, a valuable strategy for the improvement of the hyperthermic efficiency is increasing the magnetic anisotropy by doping the iron oxide with divalent Co ions. This strategy has been demonstrated to be highly efficient in the case of iron oxide nanoparticles mineralized in Human Ferritin (HFt). However, a deterioration of nanoparticles crystallinity and consequently a reduction of the hyperthermic efficiency were observed with increasing Co-doping. In this contribution, we compare two series of Co-doped iron oxide nanoparticles (Co-doping level up to 15%) mineralized into HFt and into Ferritin from the archaea Pirococcus Furiosus (PfFt), the protein structure of which differs for the nucleation sites, with the aim of increasing the crystalline quality of the inorganic cores for larger Co doping. Highly monodisperse nanoparticles of 6-7 nm were obtained in both series. The structural and magnetic characterization indicate that the PfFt series is less subjected to crystallinity deterioration with increasing Co content with respect to the HFt one. Such difference is reflected in the hyperthermic efficiency, which reaches the maximum value for different intermediate Co-doping (10% and 5% for PfFt and HFt, respectively), and goes to zero for further Co-doping increments.

Resonant Inelastic Soft X-ray Scattering Study of Co-Doped Maghemite Nanoparticles.

Cobalt ferrite nanoparticles have been attracting considerable interest in the recent years because of the large number of potential applications, including magnetic storage, magnetic fluid hyperthermia and as contrast agents for magnetic resonance imaging. Physical properties of this class of materials depend critically on a number of parameters, including crystallinity, stoichiometry and cation distribution. In this work we have performed a Resonant Inelastic soft X-ray Scattering (RIXS) study on a series of 5 nm cobalt-doped maghemite nanoparticles to obtain direct quantitative information on cation distribution as a function of cobalt doping. We found that the distribution of divalent cobalt is stable in the investigated doping range and slightly different from that of bulk, stoichiometric cobalt ferrite. These results confirm that cobalt doping can be used to finely tune the magnetic properties of nanostructured ferrites without modifying their structural integrity.

Multifunctional Nanovectors Based on Polyamidoamine Polymers for Theranostic Application.

We present multifunctional, biocompatible and biodegradable magnetic nanovectors based on different polyamidoamine (PAA) polymers tailored with different diagnostic and therapeutic properties. Using maghemite nanoparticles with average size 15.5 ± 2.8 nm prepared by thermal decomposition, superparamagnetic nanovectors were obtained by coating the nanoparticles with synthetic polymers of PAA. These have a segmented copolymer structure, and bear PAA segments containing different amount of carboxyl groups per repeating units together with PEG segments. These copolymers are thought to combine the binding properties of the carboxylated PAA segments to inorganic nanoparticles, with the stealth properties of the PEG ones. The magnetic, hyperthermal and relaxometric properties of the synthesized samples were investigated. Magnetic measurements revealed that the samples are superparamagnetic at room temperature and the overall magnetic behavior is not affected by the functionalization process. Calorimetric measurements demonstrated a good heating efficiency at alternating magnetic field parameters below the human tolerability threshold (SAR of ca. 70 W/g at 260 Hz and 10.8 kA/m). 1H-NMR relaxivities were relevant compared to the values of the commercial contrast agents over the whole investigated frequency range.

Solvothermally Driven Mn Doping and Clustering of Iron Oxide Nanoparticles for Heat Delivery Applications.

Direct interactions between nanoparticles of Mn-doped magnetite or maghemite (clearly differentiated by Raman spectroscopy) grouped in spherical clusters minimize the effect related to their characteristic magnetic dead layer at the surface. Hence, the clustering process jointly with the manganese doping renders these ferrite nanostructures very attractive as displaying increased saturation magnetization, offering, consequently, outstanding values of the specific absorption rate (SAR) for heat delivery. The whole picture for bio-related applications has been considered, with issues related to magnetic manipulation, colloidal stability, and biocompatibility.

Grafting single molecule magnets on gold nanoparticles.

The chemical synthesis and characterization of the first hybrid material composed by gold nanoparticles and single molecule magnets (SMMs) are described. Gold nanoparticles are functionalized via ligand exchange using a tetrairon(III) SMM containing two 1,2-dithiolane end groups. The grafting is evidenced by the shift of the plasmon resonance peak recorded with a UV-vis spectrometer, by the suppression of nuclear magnetic resonance signals, by X-ray photoemission spectroscopy peaks, and by transmission electron microscopy images. The latter evidence the formation of aggregates of nanoparticles as a consequence of the cross-linking ability of Fe4 through the two 1,2-dithiolane rings located on opposite sides of the metal core. The presence of intact Fe4 molecules is directly proven by synchrotron-based X-ray absorption spectroscopy and X-ray magnetic circular dichroism spectroscopy, while a detailed magnetic characterization, obtained using electron paramagnetic resonance and alternating-current susceptibility, confirms the persistence of SMM behavior in this new hybrid nanostructure.

Circular magnetoplasmonic modes in gold nanoparticles.

The quest for efficient ways of modulating localized surface plasmon resonance is one of the frontiers in current research in plasmonics; the use of a magnetic field as a source of modulation is among the most promising candidates for active plasmonics. Here we report the observation of magnetoplasmonic modes on colloidal gold nanoparticles detected by means of magnetic circular dichroism (MCD) spectroscopy and provide a model that is able to rationalize and reproduce the experiment with unprecedented qualitative and quantitative accuracy. We believe that the steep slope observed at the plasmon resonance in the MCD spectrum can be very efficient in detecting changes in the refractive index of the surrounding medium, and we give a simple proof of principle of its possible implementation for magnetoplasmonic refractometric sensing.

Gold/cobalt ferrite nanocomposite as a potential agent for photothermal therapy.

The study encompasses an investigation of optical, photothermal and biocompatibility properties of a composite consisting of golden cores surrounded by superparamagnetic CoFe2O4 nanoparticles. Accompanied with the experiment, the computational modeling reveals that each adjusted magnetic nanoparticle redshifts the plasmon resonance frequency in gold and nonlinearly increases the extinction cross-section at ~800 nm. The concentration dependent photothermal study demonstrates a temperature increase of 8.2 K and the photothermal conversion efficiency of 51% for the 100 µg/mL aqueous solution of the composite nanoparticles, when subjected to a laser power of 0.5 W at 815 nm. During an in vitro photothermal therapy, a portion of the composite nanoparticles, initially seeded at this concentration, remained associated with the cells after washing. These retained nanoparticles effectively heated the cell culture medium, resulting in a 22% reduction in cell viability after 15 min of the treatment. The composite features a potential in multimodal magneto-plasmonic therapies.

Copper sulfide nanocrystals with tunable composition by reduction of covellite nanocrystals with Cu+ ions.

Platelet-shaped copper sulfide nanocrystals (NCs) with tunable Cu stoichiometry were prepared from Cu-rich covellite (Cu1.1S) nanoplates through their reaction with a Cu(I) complex ([Cu(CH3CN)4]PF6) at room temperature. Starting from a common sample, by this approach it is possible to access a range of compositions in these NCs, varying from Cu1.1S up to Cu2S, each characterized by a different optical response: from the metallic covellite, with a high density of free carriers and strong localized surface plasmon resonance (LSPR), up to Cu2S NCs with no LSPR. In all these NCs the valency of Cu in the lattice stays always close to +1, while the average -1 valency of S in covellite gradually evolves to -2 with increasing Cu content; i.e., sulfur is progressively reduced. The addition of copper to the starting covellite NCs is similar to the intercalation of metal species in layered transition metal dichalcogenides (TMDCs); i.e., the chalcogen-chalcogen bonds holding the layers are progressively broken to make room for the intercalated metals, while their overall anion sublattice does not change much. However, differently from the TMDCs, the intercalation in covellite NCs is sustained by a change in the redox state of the anion framework. Furthermore, the amount of Cu incorporated in the NCs upon reaction is associated with the formation of an equimolar amount of Cu(II) species in solution. Therefore, the reaction scheme can be written as: Cu1.1S + 2γCu(I) → Cu1.1+γS + γCu(II).

The effect of size, shape, coating and functionalization on nuclear relaxation properties in iron oxide core-shell nanoparticles: a brief review of the situation.

In this perspective article, we present a short selection of some of the most significant case studies on magnetic nanoparticles for potential applications in nanomedicine, mainly magnetic resonance. For almost 10 years, our research activity focused on the comprehension of the physical mechanisms on the basis of the nuclear relaxation of magnetic nanoparticles in the presence of magnetic fields; taking advantage of the insights gathered over this time span, we report on the dependence of the relaxation behaviour on the chemico-physical properties of magnetic nanoparticles and discuss them in full detail. In particular, a critical review is carried out on the correlations between their efficiency as contrast agents in magnetic resonance imaging and the magnetic core of magnetic nanoparticles (mainly iron oxides), their size and shape, and the coating and solvent used for making them biocompatible and well dispersible in physiological media. Finally, the heuristic model proposed by Roch and coworkers is presented, as it was extensively adopted to describe most of the experimental data sets. The large amount of data analyzed allowed us to highlight both the advantages and limitations of the model.

1H-NMR Relaxation of Ferrite Core-Shell Nanoparticles: Evaluation of the Coating Effect.

We investigated the effect of different organic coatings on the 1H-NMR relaxation properties of ultra-small iron-oxide-based magnetic nanoparticles. The first set of nanoparticles, with a magnetic core diameter ds1 = 4.4 ± 0.7 nm, was coated with polyacrylic acid (PAA) and dimercaptosuccinic acid (DMSA), while the second set, ds2 = 8.9 ± 0.9 nm, was coated with aminopropylphosphonic acid (APPA) and DMSA. At fixed core diameters but different coatings, magnetization measurements revealed a similar behavior as a function of temperature and field. On the other hand, the 1H-NMR longitudinal r1 nuclear relaxivity in the frequency range ν = 10 kHz ÷ 300 MHz displayed, for the smallest particles (diameter ds1), an intensity and a frequency behavior dependent on the kind of coating, thus indicating different electronic spin dynamics. Conversely, no differences were found in the r1 relaxivity of the biggest particles (ds2) when the coating was changed. It is concluded that, when the surface to volume ratio, i.e., the surface to bulk spins ratio, increases (smallest nanoparticles), the spin dynamics change significantly, possibly due to the contribution of surface spin dynamics/topology.

Simple engineering of hybrid cellulose nanocrystal-gold nanoparticles results in a functional glyconanomaterial with biomolecular recognition properties.

Cellulose nanocrystal and gold nanoparticles are assembled, in a unique way, to yield a novel modular glyconanomaterial whose surface is then easily engineered with one or two different headgroups, by exploiting a robust click chemistry route. We demonstrate the potential of this approach by conjugating monosaccharide headgroups to the glyconanomaterial and show that the sugars retain their binding capability to C-type lectin receptors, as also directly visualized by cryo-TEM.

Shaping Silver Nanoparticles' Size through the Carrier Composition: Synthesis and Antimicrobial Activity.

The increasing resistance of bacteria to conventional antibiotics represents a severe global emergency for human health. The broad-spectrum antibacterial activity of silver has been known for a long time, and silver at the nanoscale shows enhanced antibacterial activity. This has prompted research into the development of silver-based nanomaterials for applications in clinical settings. In this work, the synthesis of three different silver nanoparticles (AgNPs) hybrids using both organic and inorganic supports with intrinsic antibacterial properties is described. The tuning of the AgNPs' shape and size according to the type of bioactive support was also investigated. Specifically, the commercially available sulfated cellulose nanocrystal (CNC), the salicylic acid functionalized reduced graphene oxide (rGO-SA), and the commercially available titanium dioxide (TiO2) were chosen as organic (CNC, rGO-SA) and inorganic (TiO2) supports. Then, the antimicrobial activity of the AgNP composites was assessed on clinically relevant multi-drug-resistant bacteria and the fungus Candida albicans. The results show how the formation of Ag nanoparticles on the selected supports provides the resulting composite materials with an effective antibacterial activity.

Defect-Engineering by Solvent Mediated Mild Oxidation as a Tool to Induce Exchange Bias in Metal Doped Ferrites.

The crystal site occupancy of different divalent ions and the induction of lattice defects represent an additional tool for modifying the intrinsic magnetic properties of spinel ferrites nanoparticles. Here, the relevance of the lattice defects is demonstrated in the appearance of exchange-bias and in the improvement of the magnetic properties of doped ferrites of 20 nm, obtained from the mild oxidation of core@shell (wüstite@ferrite) nanoparticles. Three types of nanoparticles (Fe0.95 O@Fe3 O4 , Co0.3 Fe0.7 O@Co0.8 Fe2.2 O4 and Ni0.17 Co0.21 Fe0.62 O@Ni0.4 Co0.3 Fe2.3 O4 ) are oxidized. As a result, the core@shell morphology is removed and transformed in a spinel-like nanoparticle, through a topotactic transformation. This study shows that most of the induced defects in these nanoparticles and their magnetic properties are driven by the inability of the Co(II) ions at the octahedral sites to migrate to tetrahedral sites, at the chosen mild oxidation temperature. In addition, the appearance of crystal defects and antiphase boundaries improves the magnetic properties of the starting compounds and leads to the appearance of exchange bias at room temperature. These results highlight the validity of the proposed method to impose novel magnetic characteristics in the technologically relevant class of nanomaterials such as spinel ferrites, expanding their potential exploitation in several application fields.

Proton Therapy, Magnetic Nanoparticles and Hyperthermia as Combined Treatment for Pancreatic BxPC3 Tumor Cells.

We present an investigation of the effects on BxPC3 pancreatic cancer cells of proton therapy combined with hyperthermia, assisted by magnetic fluid hyperthermia performed with the use of magnetic nanoparticles. The cells' response to the combined treatment has been evaluated by means of the clonogenic survival assay and the estimation of DNA Double Strand Breaks (DSBs). The Reactive Oxygen Species (ROS) production, the tumor cell invasion and the cell cycle variations have also been studied. The experimental results have shown that the combination of proton therapy, MNPs administration and hyperthermia gives a clonogenic survival that is much smaller than the single irradiation treatment at all doses, thus suggesting a new effective combined therapy for the pancreatic tumor. Importantly, the effect of the therapies used here is synergistic. Moreover, after proton irradiation, the hyperthermia treatment was able to increase the number of DSBs, even though just at 6 h after the treatment. Noticeably, the magnetic nanoparticles' presence induces radiosensitization effects, and hyperthermia increases the production of ROS, which contributes to cytotoxic cellular effects and to a wide variety of lesions including DNA damage. The present study indicates a new way for clinical translation of combined therapies, also in the vision of an increasing number of hospitals that will use the proton therapy technique in the near future for different kinds of radio-resistant cancers.