Targeted nanostructured lipid carriers for doxorubicin oral delivery.

The treatment with anticancer drugs remains a challenge, as available drugs still entail the risk of deleterious off-target effects. The present study describes folic acid conjugated nanostructured lipid carriers (NLCs) as an effective doxorubicin delivery approach targeted to breast cancer cells. Two distinct NLCs formulations were designed and optimized leading to an encapsulation efficiency over than 65%. Cytotoxic and targeting potential of NLCs were studied in vitro, using MDA-MB-231 cell line. Results showed an enhanced cellular uptake of conjugated NLCs. In vitro release studies, mimicking the path in the body after oral administration, show that all formulations would reach the tumor microenvironment bearing 50% of the encapsulated doxorubicin. Moreover, NLCs demonstrated storage stability at 25 °C for at least 42 days. Overall, results revealed that the developed NLCs enable the possibility of oral administration and are a promising approach for the targeted delivery of doxorubicin to breast cancer cells.

Evaluation of the toxicity of nickel nanowires to freshwater organisms at concentrations and short-term exposures compatible with their application in water treatment.

In order to understand the potential impacts of nickel nanowires (Ni NWs) after reaching the aquatic environment, this research evaluated the toxicity of Ni NWs with different lengths (≤ 1.1, ≤11 and ≤ 80 µm) for several floating, planktonic and nektonic freshwater organisms. In this work, Ni NWs were synthesized by electrodeposition using anodized aluminum oxide (AAO) membranes. The toxicity of the NWs was assessed using a battery of aquatic species representative of key functions at the ecosystem level: the bacterium Aliivibrio fischeri, the algae Raphidocelis subcapitata, the macrophyte Lemna minor, the crustacean Daphnia magna and the zebrafish Danio rerio. Results indicated that for the concentrations tested (up to 2.5 mg L-1) the synthesized Ni NWs showed low toxicity. And although no lethal toxicity was observed for D. magna, at a sublethal level the feeding activity of the freshwater cladoceran was severely affected after exposure to Ni NWs. These findings showed that NWs can be accumulated in the gut of D. magna, even during a short exposure (24 h) directly impairing Daphnia nutrition and eventually populations growth. Consequently, this can also contribute to trophic transfer of NWs along the food chain. According to our results the toxicity of Ni NW may be mainly attributed to physical effects rather than chemical effects of Ni ions, considering that the concentrations of Ni NWs tested in this study were well below the toxicity thresholds reported in the literature for Ni ions and for Ni NMs.

Tuning the magnetic properties of multisegmented Ni/Cu electrodeposited nanowires with controllable Ni lengths.

The fabrication of segmented Ni/Cu nanowires (NWs), with tunable structural and magnetic properties, is reported. A potentiostatic electrodeposition method with a single electrolytic bath has been used to fabricate multisegmented Ni/Cu NWs inside a highly hexagonally ordered anodic nanoporous alumina membrane, with diameters of 50 nm and Ni segment lengths (L Ni) tuned from 10 nm up to 140 nm. The x-ray diffraction results evidenced a strong dependence of the Ni NWs crystallographic face-centered-cubic (fcc) texture along the [220] direction on the aspect ratio of the NWs. The magnetic behavior of the multisegmented Ni/Cu NW arrays, as a function of the magnetic field and temperature, is also studied and correlated with their structural and morphological properties. Micromagnetic simulations, together with the experimental results, showed a dominant antiferromagnetic coupling between Ni segments along the wire length for small low aspect-ratio magnetic segments. When increasing the Ni segments' length, the magnetic interactions between these along the wire became stronger, favouring a ferromagnetic coupling. The Curie temperature of the NWs was also found to strongly depend on the Ni magnetic segment length. Particularly the Curie temperature was found to be reduced 75 K for the 20 nm Ni segments, following the finite-size scaling relation with ξ 0 = 8.1 Å and γ = 0.48. These results emphasize the advantages of using a template assisted method to electrodeposit multilayer NWs, as it allows an easy tailor of the respective morphological, chemical, structural and magnetic properties.

Modeling the Growth Kinetics of Anodic TiO2 Nanotubes.

The fundamental understanding of the barrier layer (δ(b)) growth in TiO2 nanotubes (NTs) is here established and compared with the classical metal oxidation theory from Mott and Cabrera. The role of δ(b) in the anodization of TiO2 NTs under different applied potentials and times was analyzed using scanning transmission electron microscopy (STEM). Contrary to the well-known case of anodic aluminum oxide, we found that δ(b) of TiO2 NTs progressively grows over time due to the nonsteady anodization regime. We then establish a relation between the phenomenological growth of the barrier layer with time and applied voltage, δ(b)(V,t) using the high-field Mott and Cabrera conduction theory. The developed model was found to be in excellent agreement with the experimental data from both STEM and anodization curves. On the basis of these results, the relationship between δ(b) and the anodization time and potential can now be quantitatively understood.

Tailoring the Ti surface via electropolishing nanopatterning as a route to obtain highly ordered TiO2 nanotubes.

Highly ordered TiO2 nanotubes (NTs) were synthesized by the electrochemical anodization of Ti foils subjected to electropolishing (EP) pre-treatment. We found that the Ti surface roughness plays an important role in the onset of pore nucleation in enhancing the local focusing effect of the electrical field. Additionally, EP induces the formation of dimple structures on the metal surface, which can work as a pre-pattern prior to anodization. These shallow ripples lead to a preferentially ordered pore nucleation, offering an organizational improvement of the anodic oxide NTs. We found that, depending on the EP applied potential, the roughness and the spatial period of the ripple-like structures varies from 8-2 nm and from 122-30 nm, respectively. Such tuning allowed us to focus on the influence of the initial Ti pre-surface topography features on the NTs' length, organization, and hexagonal arrangement quality, as well as diameter and density. Our results show that an EP under 10 V is the most suitable to obtain a small Ti surface roughness, the largest NT length (40% enhancement), and the effective improvement of the ordered hexagonal NTs' arrays over larger areas. Furthermore, the NTs' dimensions (pore diameters and density) were also found to depend on the initial Ti surface topography. The use of optimized EP allows us to obtain highly hexagonal self-ordered samples at a reduced time and cost.

Angular first-order reversal curves: an advanced method to extract magnetization reversal mechanisms and quantify magnetostatic interactions.

The magnetic properties of ordered hexagonal arrays of Co nanowires (NWs) and nanotubes (NTs) with diameters of 50 nm and interwire/tube distances of 105 nm were studied using first-order reversal curves (FORCs). We report an advanced analysis of angle dependent first-order reversal curves (AFORCs), measured by changing the angle of the applied magnetic field from θ = 0° (parallel to the wire/tube axis) to 90° (perpendicular). This method allowed us to determine the magnetization reversal mode and to retrieve quantitative information on the magnetostatic interactions between NWs and between NTs. In particular, we found a sharp increase in the coercivity distribution of the NT arrays for θ > 70°, which is attributed to a transition between vortex and transverse reversal modes. Local magnetic interactions are found to prevail in the Co NT arrays, steadily increasing from θ = 0° to 90°. However, in the Co NW arrays the mean magnetic interactions decrease as θ increases, going from ones similar to local interactions to ones smaller than them.

Co nanostructures in ordered templates: comparative FORC analysis.

A comparative study on the structural and magnetic properties of highly ordered hexagonal arrays of Co nanoholes, nanowires, nanopillars and nanotubes, with tuned pore/wire/tube diameters, is here presented. The magnetic interactions and their dependence on the geometric features of the arrays were studied using first-order reversal curves (FORCs). For all nanostructures we observe an increase of the magnetostatic interactions with the templates' pore diameter, with the higher (smaller) values found for the nanowire (nanohole) arrays. For the smallest diameters studied (35 nm), all types of arrays could be considered as almost isolated nanostructures, where local interactions prevail. In particular, both nanotube and nanohole arrays exhibit considerable local magnetostatic interactions coming from the stray fields within each void or empty core. On the other hand, the coercivity is found to decrease with diameter for the elongated nanostructures, while it increases with the pore diameter for the nanohole arrays. This behavior is associated with the magnetization reversal mechanisms present in each array. This work highlights a versatile route to tailor the size, geometrical arrangement and magnetostatic interactions of ordered arrays and demonstrates their importance for the tuning of the magnetic behavior of nanometric devices.

Correlations among magnetic, electrical and magneto-transport properties of NiFe nanohole arrays.

In this work, we use anodic aluminum oxide (AAO) templates to build NiFe magnetic nanohole arrays. We perform a thorough study of their magnetic, electrical and magneto-transport properties (including the resistance R(T), and magnetoresistance MR(T)), enabling us to infer the nanohole film morphology, and the evolution from granular to continuous film with increasing thickness. In fact, different physical behaviors were observed to occur in the thickness range of the study (2 nm < t < 100 nm). For t < 10 nm, an insulator-to-metallic crossover was visible in R(T), pointing to a granular film morphology, and thus being consistent with the presence of electron tunneling mechanisms in the magnetoresistance. Then, for 10 nm < t < 50 nm a metallic R(T) allied with a larger anisotropic magnetoresistance suggests the onset of morphological percolation of the granular film. Finally, for t > 50 nm, a metallic R(T) and only anisotropic magnetoresistance behavior were obtained, characteristic of a continuous thin film. Therefore, by combining simple low-cost bottom-up (templates) and top-down (sputtering deposition) techniques, we are able to obtain customized magnetic nanostructures with well-controlled physical properties, showing nanohole diameters smaller than 35 nm.

Probing the quality of Ni filled nanoporous alumina templates by magnetic techniques.

Pulsed electrodeposition prepared porous alumina templates with Ni nanowires pore filling ranged from 1 to 100%, depending on the alumina barrier-layer thickness, were probed by continuous wave ferromagnetic resonance at room temperature. For completely filled samples, a single resonance peak was observed in the whole range of angles between the applied magnetic field and normal to the sample plane. Its position was described by Kittel formula that takes into account shape anisotropy of individual Ni wires and dipolar interactions between them. For the samples with lower pore filling the effective anisotropy field decreased and the resonance linewidth in the perpendicular configuration increased. Also a quite intense second peak was observed at lower fields for these samples. These changes are associated with reduction of pore filling percentage that can lead to decrease of dipolar interactions between nanowires and to appearance of magnetic inhomogeneities inside wires.

Tailoring the physical properties of thin nanohole arrays grown on flat anodic aluminum oxide templates.

The introduction of voids in a magnetic thin-film alters the stray field distribution and enables the tailoring of the corresponding physical properties. Here we present a detailed study on thin magnetic nanohole arrays (NhAs) grown on top of hexagonally-ordered anodic aluminum oxide (AAO) substrates. We address the effect of AAO topography on the corresponding electrical and magneto-transport properties. Optimization of the AAO topography led to NhAs with improved resistance and magnetoresistance responses, while retaining their most important feature of enhanced coercivity. This opens new pathways for the growth of more complex structures on AAO substrates, a crucial aspect for their technological viability.

Influence of the rest pulse duration in pulsed electrodeposition of Fe nanowires.

Highly uniform iron nanowires were synthesized in porous anodic alumina, through a pulsed electrodeposition method. The effect of the rest pulse duration in the deposition quality was systematically investigated, being the best duration found at 0.6 s with 91.9% of pores filled. A methodology of surface response design of experiment was conducted to find the optimum predicted value for the rest pulse duration, by controlling the following experimental parameters/variables: current density, electrolyte concentration and temperature. The influence of the rest pulse in the grain size of the iron nanowires was also studied trough X-ray diffraction patterns. A numerical simulation of the concentration evolution along a nanopore was performed, allowing to achieve a deeper understanding of the importance of the rest pulse in the NW electrodeposition.

Tunning pore filling of anodic alumina templates by accurate control of the bottom barrier layer thickness.

The role of the alumina barrier layer thickness (δ(b)) on the growth of Ni nanowires (NWs) in porous anodic alumina (PAA) has been revealed. By varying the final anodization voltage to form dendrites at the bottom of the nanoporous structure, we are able to optimize δ(b) (in the 2-16 nm range), allowing us to obtain a Ni pore filling percentage (f(p)) of almost 100% for δ(b) = 10 nm. However, deviations from this optimal δ(b)-value led to a strong decrease of f(p). Moreover, an increase of the electrodeposition efficiency (EE) and NW homogeneity was also verified for δ(b) up to 10 nm. Such increase in nominal δ(b) leads to a consistent growth rate in all pores and consequently a complete and uniform nanopore filling. On the other hand, the decrease in electrodeposition efficiency visible for δ(b) > 10 nm is related with hydrogen evolution and dielectric breakdown of the insulator layer due to the required high deposition voltages. Non-uniform NW growth is then visible, with the consequent decrease in f(p). The control of the pore filling and length homogeneity of the fabricated 1D metallic nanostructures, combined with the ability to adjust the pore dimensions of PAA, can bring novel approaches for the fabrication of nano-objects and thus exciting new applications.

Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge.

Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Rapid synthesis of ordered manganite nanotubes by microwave irradiation in alumina templates.

Highly ordered La2/3Ca1/3MnO3 nanotube arrays were successfully synthesized by a simple and rapid process, combining nanoporous alumina template-assisted synthesis with microwave irradiation. The method offers a quick hands-on route to produce manganite bulk sample and nanotube arrays at relative low-temperatures. We obtain thin wall nanotubes of uniform diameter of 80 nm. The growth mechanism of nanotubes is briefly discussed. Magnetic measurements indicate that the ferromagnetic transition temperature T(c) of the nanotubes is depleted with respect to its bulk counterpart possibly due to the geometric confinement imposed by the thin wall of the nanotubes.