Effects of layer-by-layer coating on activated carbon electrodes for capacitive deionization.

Recently, the need for obtaining, reusing, or purifying water has become a crucial issue. The capacitive deionization (CDI) method, which is based on the electric double layer (EDL) concept, can be applied to ion adsorption from an aqueous solution. This process is carried out by applying a potential difference to highly porous electrodes while pumping salty solution between them, partially removing the ions present in the solution and keeping them in the surface of the electrodes. The use of coated carbon electrodes with one polyelectrolyte layer, turning them into "soft electrodes" (SEs), has been proved to improve the efficiency of the system with respect to its original configuration. In this work, we investigate the effect on the ion adsorption and the efficiency of the process when implementing the coating technique known as layer-by-layer (LbL) on the electrode. This consists in successively coating the electrode surfaces with polyelectrolyte layers, alternating their charge polarity in each step. We tested the effect of the number of layers deposited, as well as the impact of this technique by using different carbons. We found that the second polyelectrolyte layer adheres more than the first layer, serving as a support or seed when it is not dense and uniformly distributed. In contrast, if the first layer is well adhered, a third layer is needed to observe improvements in adsorption and process efficiency. The adsorption of the polymer layers depends in any instance on the porosity of the carbon.

Fluid restriction versus volume expansion in children with diarrhea-associated HUS: a retrospective observational study.

BACKGROUND: Fifty percent of patients with typical diarrhea-associated hemolytic uremic syndrome (D+HUS) require kidney replacement therapy (KRT). In these patients, dehydration worsens disease prognosis. We evaluated dialysis requirement, presence of seizures, and mortality rate among patients diagnosed with D+HUS treated with volume expansion (VE) versus fluid restriction (FR). METHODS: Thirty-five patients with D+HUS were enrolled; 16 received VE and 19 were historical patients who received conventional FR. RESULTS: Upon admission or during treatment, neither group presented evidence of fluid overload. The VE group received higher volumes of saline (VE 27 ml/kg [10-30] over a 3-h period vs. FR 0 ml), had higher urine output after 12 h (VE vs. FR: OR 6.2 [1.2-41.6], P = 0.03), and required less dialysis (VE 2 [12.5%, CI 95% 0-29] vs. FR 9 [47.4%, CI 95% 24-70], P = 0.035). The VE group had an absolute risk reduction of 0.34 (CI 95% 0.07-0.63); hence, three patients treated with VE were required to avoid one KRT. VE also corrected initial hyponatremia and maintained serum sodium within normal ranges. No statistical differences were observed regarding number of patients with seizures (P = 0.08) or mortality (P = 1.0). CONCLUSIONS: VE markedly reduces the number of patients requiring KRT and keeps serum sodium within a normal range. We propose to initially hydrate every patient with D+HUS and without signs of fluid overload, with 10 ml/kg/h 0.9% saline solution IV, over a 3-h period. Afterwards, if urine output is ≥ 0.5 ml/kg/h, it is recommended to not dialyze and continue IV hydration schedule with isotonic (D5) saline solution, according to their needs.

Use of Soft Electrodes in Capacitive Deionization of Solutions.

All efforts to obtain, reuse or purify water are extremely significant for society. Recently, researchers have begun to delve in an idea born decades ago: the desalination of water using highly porous electrodes. It is based on a fundamental aspect of electrical double layers, namely, their huge capacitance. The ions of a solution can be partially removed under the application of an electric field when the solution fills the space between porous electrodes, either bare (CDI, or capacitive deionization), coated with ionic exchange membranes (MCDI) or chemically treated (inverted-CDI or i-CDI). One of the challenges of the last years was to explore new materials and arrangements to improve the efficiency of the system. In this work, we propose a new approach inspired in the electrokinetics of soft particles: a layer of polyelectrolyte (cationic on one electrode, anionic on the opposite one) coats the carbon electrodes, converting them in a sort of "soft" electrode pair. We present a theoretical model and a set of experiments showing how soft electrodes can be successfully employed in capacitive deionization.

Electric birefringence spectroscopy of montmorillonite particles.

Electric birefringence (EB) of suspensions of anisotropic particles can be considered an electrokinetic phenomenon in a wide sense, as both liquid motions and polarization of the electrical double layer (EDL) of the particles participate in the process of particle orientation under the applied field. The EB spectrum can be exploited for obtaining information on the dimensions, average value and anisotropy of the surface conductivity of the particles, and the concentration and Maxwell-Wagner polarization of the EDLs. It is thus a highly informative technique, applicable to non-spherical particles. In this paper, we investigate the birefringent response of plate-like montmorillonite particles as a function of the frequency and amplitude of the applied AC electric field, for different compositions (pH, ionic strength, particle concentration) of the suspensions. The transient electric birefringence (i.e., the decay of the refractive index anisotropy with time when the field is switched off) is used for estimating the average dimensions of the particle axes, by modeling it as an oblate spheroid. The obtained values are very similar to those deduced from electron microscopy determinations. The frequency spectra show a very distinct behaviour at low (on the order of a few Hz) and high (up to several MHz) frequencies: the α and Maxwell-Wagner-O'Konski relaxations, characteristic of EDLs, are detected at frequencies above 10 kHz, and they can be well explained using electrokinetic models for the polarization of EDLs. At low frequencies, in contrast, the birefringence changes to negative, an anomalous response meaning that the particles tend to orient with their symmetry axis parallel to the field. This anomaly is weaker at basic pH values, high ionic strengths and low concentrations. The results can be explained by considering the polydispersity of real samples: the fastest particles redistribute around the slowest ones, inducing a hydrodynamic torque opposite to that of the field, in close similarity with the results previously described for the mixtures of anisometric particles with small amounts of spherical nanoparticles.

Lipid transfer between submicrometer sized Pickering ISAsome emulsions and the influence of added hydrogel.

Transfer of lipids between droplets in Pickering emulsions has been studied by time-resolved small-angle X-ray scattering (SAXS). The special features of self-assembled liquid-crystalline phases have been applied to examine the kinetics of internal phase reorganization imposed by lipid release and uptake by the droplets. The findings reveal faster transfer kinetics in Pickering emulsions than in emulsions stabilized with Pluronic F127. It is shown that the transfer kinetics can be accelerated by adding free surfactant to the dispersions and that this acceleration becomes more dominant when micelles are formed. The effect of immobilization of the droplets has been studied by incorporating them into the appropriate hydrogel network. The droplets are arrested, and the transfer slows down significantly at high enough concentrations of the hydrogel where nonergodic systems are obtained.

Temperature effects on energy production by salinity exchange.

In recent years, the capacitance of the interface between charged electrodes and ionic solutions (the electric double layer) has been investigated as a source of clean energy. Charge is placed on the electrodes either by means of ion-exchange membranes or of an external power source. In the latter method, net energy is produced by simple solution exchange in open circuit, due to the associated decrease in the capacitance of the electric double layer. In this work, we consider the change in capacitance associated with temperature variations: the former decreases when temperature is raised, and, hence, a cycle is possible in which some charge is put on the electrode at a certain potential and returned at a higher one. We demonstrate experimentally that it is thus viable to obtain energy from electric double layers if these are successively contacted with water at different temperatures. In addition, we show theoretically and experimentally that temperature and salinity variations can be conveniently combined to maximize the electrode potential increase. The resulting available energy is also estimated.

Artificial intelligence model for tumoral clinical decision support systems.

BACKGROUND AND OBJECTIVE: Comparative diagnostic in brain tumor evaluation makes possible to use the available information of a medical center to compare similar cases when a new patient is evaluated. By leveraging Artificial Intelligence models, the proposed system is able of retrieving the most similar cases of brain tumors for a given query. The primary objective is to enhance the diagnostic process by generating more accurate representations of medical images, with a particular focus on patient-specific normal features and pathologies. A key distinction from previous models lies in its ability to produce enriched image descriptors solely from binary information, eliminating the need for costly and difficult to obtain tumor segmentation. METHODS: The proposed model uses Artificial Intelligence to detect patient features to recommend the most similar cases from a database. The system not only suggests similar cases but also balances the representation of healthy and abnormal features in its design. This not only encourages the generalization of its use but also aids clinicians in their decision-making processes. This generalization makes possible for future research in different medical diagnosis areas with almost not any change in the system. RESULTS: We conducted a comparative analysis of our approach in relation to similar studies. The proposed architecture obtains a Dice coefficient of 0.474 in both tumoral and healthy regions of the patients, which outperforms previous literature. Our proposed model excels at extracting and combining anatomical and pathological features from brain Magnetic Resonances (MRs), achieving state-of-the-art results while relying on less expensive label information. This substantially reduces the overall cost of the training process. Our findings highlight the significant potential for improving the efficiency and accuracy of comparative diagnostics and the treatment of tumoral pathologies. CONCLUSIONS: This paper provides substantial grounds for further exploration of the broader applicability and optimization of the proposed architecture to enhance clinical decision-making. The novel approach presented in this work marks a significant advancement in the field of medical diagnosis, particularly in the context of Artificial Intelligence-assisted image retrieval, and promises to reduce costs and improve the quality of patient care using Artificial Intelligence as a support tool instead of a black box system.

Formulative Study and Characterization of Novel Biomaterials Based on Chitosan/Hydrolyzed Collagen Films.

To date, the need for biomaterials capable of improving the treatment of chronic skin wounds remains a clinical challenge. The aim of the present work is to formulate and characterize chitosan (Cs)/hydrolyzed collagen (HC) films as potential biomaterials with improved mechanical and hydration performances compared to single component formulations. Films were made by the solvent casting method, with or without glycerin and/or PEG1500 as plasticizers, resulting in a total of eight formulations. All films were characterized by their physico-chemical characteristics and their mechanical and hydration features. A full factorial design was also used to statistically assess the effect of HC concentration, type and concentration of plasticizers and their possible interactions on mechanical and swelling behaviors. Solid state characterization confirmed the hybrid nature of the films, with suggested electrostatic interactions between Cs and HC. Mechanical and swelling properties, along with the analysis of the experimental design, allowed the identification of formulations containing high HC concentration (2% w/v) and glycerin or glycerin/PEG1500 as more suitable candidates for skin wound treatment. Finally, viability assay of immortalized human keratinocytes (HaCaT) showed no statistical differences in cell survival compared to the complete culture medium, suggesting their potential as a promising tool for biomedical applications.

Lipid transfer in oil-in-water isasome emulsions: influence of arrested dynamics of the emulsion droplets entrapped in a hydrogel.

The transfer kinetics of lipids between internally self-assembled droplets of O/W emulsions is studied. The droplets (isasomes) consist of various liquid-crystalline phases or W/O microemulsions stabilized by a polymeric stabilizer F127. The various internal phases were identified by the relative peak positions in the small-angle X-ray scattering (SAXS) curves. An arrested system composed of isasomes embedded in a gel matrix actually provides an additional possibility to control these systems in terms of the release of various host molecules. These experiments have been applied to examine the kinetics of the internal phase reorganization imposed by the lipids' release and uptake by the droplets embedded in a κ-carrageenan (KC) hydrogel network. Increasing the concentration of the gelling agent slows down the transfer from one droplet to the other through the aqueous phase. We examined the region where the free diffusion is stopped. i.e., the point where the system changes from the ergodic to the nonergodic state and the kinetics is essentially slowed down. This effect can be balanced by the addition of small amounts of free polymeric stabilizer, which speeds up the kinetics. This is even possible in the case of highly arrested dynamics of the emulsion droplets, as found for the highest KC hydrogel concentrations forming nonergodic systems.

Combined Magnetic Hyperthermia and Photothermia with Polyelectrolyte/Gold-Coated Magnetic Nanorods.

Magnetite nanorods (MNRs) are synthesized based on the use of hematite nanoparticles of the desired geometry and dimensions as templates. The nanorods are shown to be highly monodisperse, with a 5:1 axial ratio, and with a 275 nm long semiaxis. The MNRs are intended to be employed as magnetic hyperthermia and photothermia agents, and as drug vehicles. To achieve a better control of their photothermia response, the particles are coated with a layer of gold, after applying a branched polyethyleneimine (PEI, 2 kDa molecular weight) shell. Magnetic hyperthermia is performed by application of alternating magnetic fields with frequencies in the range 118-210 kHz and amplitudes up to 22 kA/m. Photothermia is carried out by subjecting the particles to a near-infrared (850 nm) laser, and three monochromatic lasers in the visible spectrum with wavelengths 480 nm, 505 nm, and 638 nm. Best results are obtained with the 505 nm laser, because of the proximity between this wavelength and that of the plasmon resonance. A so-called dual therapy is also tested, and the heating of the samples is found to be faster than with either method separately, so the strengths of the individual fields can be reduced. Due to toxicity concerns with PEI coatings, viability of human hepatoblastoma HepG2 cells was tested after contact with nanorod suspensions up to 500 µg/mL in concentration. It was found that the cell viability was indistinguishable from control systems, so the particles can be considered non-cytotoxic in vitro. Finally, the release of the antitumor drug doxorubicin is investigated for the first time in the presence of the two external fields, and of their combination, with a clear improvement in the rate of drug release in the latter case.

Embedding Biomimetic Magnetic Nanoparticles Coupled with Peptide AS-48 into PLGA to Treat Intracellular Pathogens.

Among the strategies employed to overcome the development of multidrug-resistant bacteria, directed chemotherapy combined with local therapies (e.g., magnetic hyperthermia) has gained great interest. A nano-assembly coupling the antimicrobial peptide AS-48 to biomimetic magnetic nanoparticles (AS-48-BMNPs) was demonstrated to have potent bactericidal effects on both Gram-positive and Gram-negative bacteria when the antimicrobial activity of the peptide was combined with magnetic hyperthermia. Nevertheless, intracellular pathogens remain challenging due to the difficulty of the drug reaching the bacterium. Thus, improving the cellular uptake of the nanocarrier is crucial for the success of the treatment. In the present study, we demonstrate the embedding cellular uptake of the original nano-assembly into THP-1, reducing the toxicity of AS-48 toward healthy THP-1 cells. We optimized the design of PLGA[AS-48-BMNPs] in terms of size, colloidal stability, and hyperthermia activity (either magnetic or photothermal). The stability of the nano-formulation at physiological pH values was evaluated by studying the AS-48 release at this pH value. The influence of pH and hyperthermia on the AS-48 release from the nano-formulation was also studied. These results show a slower AS-48 release from PLGA[AS-48-BMNPs] compared to previous nano-formulations, which could make this new nano-formulation suitable for longer extended treatments of intracellular pathogens. PLGA[AS-48-BMNPs] are internalized in THP-1 cells where AS-48 is liberated slowly, which may be useful to treat diseases and prevent infection caused by intracellular pathogens. The treatment will be more efficient combined with hyperthermia or photothermia.

Modulation of the Magnetic Hyperthermia Response Using Different Superparamagnetic Iron Oxide Nanoparticle Morphologies.

The use of magnetic nanoparticles in hyperthermia, that is, heating induced by alternating magnetic fields, is gaining interest as a non-invasive, free of side effects technique that can be considered as a co-adjuvant of other cancer treatments. Having sufficient control on the field characteristics, within admissible limits, the focus is presently on the magnetic material. In the present contribution, no attempt has been made of using other composition than superparamagnetic iron oxide nanoparticles (SPION), or of applying surface functionalization, which opens a wider range of choices. We have used a hydrothermal synthesis route that allows preparing SPION nanoparticles in the 40 nm size range, with spherical, cuboidal or rod-like shapes, by minor changes in the synthesis steps. The three kinds of particles (an attempt to produce star-shaped colloids yielded hematite) were demonstrated to have the magnetite (or maghemite) crystallinity. Magnetization cycles showed virtually no hysteresis and demonstrated the superparamagnetic nature of the particles, cuboidal ones displaying saturation magnetization comparable to bulk magnetite, followed by rods and spheres. The three types were used as hyperthermia agents using magnetic fields of 20 kA/m amplitude and frequency in the range 136-205 kHz. All samples demonstrated to be able to raise the solution temperature from room values to 45 °C in a mere 60 s. Not all of them performed the same way, though. Cuboidal magnetic nanoparticles (MNPs) displayed the maximum heating power (SAR or specific absorption rate), ranging in fact among the highest reported with these geometries and raw magnetite composition.

Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles.

MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. However, the current clinical application of magnetic hyperthermia is limited due to the fact that, in order to be able to reach an effective temperature at the target site, relatively high nanoparticle concentration, as well as high magnetic field strength and/or AC frequency are needed. In the present study, the potential of BMNPs to increase the temperature upon irradiation of a laser beam in the near infrared, at a wavelength at which tissues become partially transparent, is explored. Moreover, our results also demonstrate the synergy between photothermia and chemotherapy in terms of drug release and cytotoxicity, by using BMNPs functionalized with doxorubicin, and the effectiveness of this combination therapy against tumor cells in in vitro experiments. Therefore, the findings of the present study open the possibility of a novel, alternative approach to fight localized tumors.

Enhanced Cytotoxic Effect of TAT-PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia.

The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT-PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm2). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT-PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments.

Corrosion Prediction of Weathered Galvanised Structures Using Machine Learning Techniques.

Galvanised steel atmospheric corrosion is a complex multifactorial phenomenon that globally affects many structures, equipment, and sectors. Moreover, the International Organization of Standardization (ISO) standards require specific pollutant depositions values for any atmosphere classification or corrosion loss prediction result. The aim of this research is to develop predictive models to estimate corrosion loss based on easily worldwide available parameters. Experimental data from internationally validated studies were used for the data mining process, basing their characterisation on seven globally accessible qualitative and quantitative variables. Self-Organising Maps including both supervised and unsupervised layers were used to predict first-year corrosion loss, its corrosivity categories, and an uncertainty range. Additionally, a formula optimised with Newton's method has been proposed for extrapolating these results to long-term results. The predictions obtained were compared with real values using Euclidean distances to know its similarity degree, offering high prediction performance. Specifically, evaluation results showed an average saving of up to 16% in coatings using these predictions. Therefore, using the proposed models reduces the uncertainty of the final structures state by predicting their material loss, avoiding initial over-dimensioning of structures, and meeting the principles of efficiency and sustainability, thus reducing costs.

Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles.

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here.

Poly(ethylene-imine)-Functionalized Magnetite Nanoparticles Derivatized with Folic Acid: Heating and Targeting Properties.

Magnetite nanoparticles (MNPs) coated by branched poly (ethylene-imine) (PEI) were synthesized in a one-pot. Three molecular weights of PEI were tested, namely, 1.8 kDa (sample MNP-1), 10 kDa (sample MNP-2), and 25 kDa (sample MNP-3). The MNP-1 particles were further functionalized with folic acid (FA) (sample MNP-4). The four types of particles were found to behave magnetically as superparamagnetic, with MNP-1 showing the highest magnetization saturation. The particles were evaluated as possible hyperthermia agents by subjecting them to magnetic fields of 12 kA/m strength and frequencies ranging between 115 and 175 kHz. MNP-1 released the maximum heating power, reaching 330 W/g at the highest frequency, in the high side of reported values for spherical MNPs. In vitro cell viability assays of MNP-1 and MNP-4 against three cell lines expressing different levels of FA receptors (FR), namely, HEK (low expression), and HeLa (high expression), and HepG2 (high expression), demonstrated that they are not cytotoxic. When the cells were incubated in the presence of a 175 kHz magnetic field, a significant reduction in cell viability and clone formation was obtained for the high expressing FR cells incubated with MNP-4, suggesting that MNP-4 particles are good candidates for magnetic field hyperthermia and active targeting.

Nanoformulation Design Including MamC-Mediated Biomimetic Nanoparticles Allows the Simultaneous Application of Targeted Drug Delivery and Magnetic Hyperthermia.

The design of novel nanomaterials that can be used as multifunctional platforms allowing the combination of therapies is gaining increased interest. Moreover, if this nanomaterial is intended for a targeted drug delivery, the use of several guidance methods to increase guidance efficiency is also crucial. Magnetic nanoparticles (MNPs) allow this combination of therapies and guidance strategies. In fact, MNPs can be used simultaneously as drug nanocarriers and magnetic hyperthermia agents and, moreover, they can be guided toward the target by an external magnetic field and by their functionalization with a specific probe. However, it is difficult to find a system based on MNPs that exhibits optimal conditions as a drug nanocarrier and as a magnetic hyperthermia agent. In this work, a novel nanoformulation is proposed to be used as a multifunctional platform that also allows dual complementary guidance. This nanoformulation is based on mixtures of inorganic magnetic nanoparticles (M) that have been shown to be optimal hyperthermia agents, and biomimetic magnetic nanoparticles (BM), that have been shown to be highly efficient drug nanocarriers. The presence of the magnetosome protein MamC at the surface of BM confers novel surface properties that allow for the efficient and stable functionalization of these nanoparticles without the need of further coating, with the release of the relevant molecule being pH-dependent, improved by magnetic hyperthermia. The BM are functionalized with Doxorubicin (DOXO) as a model drug and with an antibody that allows for dual guidance based on a magnetic field and on an antibody. The present study represents a proof of concept to optimize the nanoformulation composition in order to provide the best performance in terms of the magnetic hyperthermia agent and drug nanocarrier.

Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model.

Biomimetic magnetic nanoparticles mediated by magnetosome proteins (BMNPs) are potential innovative tools for cancer therapy since, besides being multifunctional platforms, they can be manipulated by an external gradient magnetic field (GMF) and/or an alternating magnetic field (AMF), mediating targeting and hyperthermia, respectively. We evaluated the cytocompatibility/cytotoxicity of BMNPs and Doxorubicin (DOXO)-BMNPs in the presence/absence of GMF in 4T1 and MCF-7 cells as well as their cellular uptake. We analyzed the biocompatibility and in vivo distribution of BMNPs as well as the effect of DOXO-BMNPs in BALB/c mice bearing 4T1 induced mammary carcinomas after applying GMF and AMF. Results: GMF enhanced the cell uptake of both BMNPs and DOXO-BMNPs and the cytotoxicity of DOXO-BMNPs. BMNPs were biocompatible when injected intravenously in BALB/c mice. The application of GMF on 4T1 tumors after each of the repeated (6×) iv administrations of DOXO-BMNPs enhanced tumor growth inhibition when compared to any other treatment, including that with soluble DOXO. Moreover, injection of DOXO-BMNPs in the tumor combined with application of an AMF resulted in a significant tumor weight reduction. These promising results show the suitability of BMNPs as magnetic nanocarriers for local targeted chemotherapy and as local agents for hyperthermia.

Reactive oxygen species (ROS) production in HepG2 cancer cell line through the application of localized alternating magnetic field.

Recent studies have shown the potential of magnetic hyperthermia in cancer treatments. However, the underlying mechanisms involved have not been yet fully described. In particular, the cell death related to magnetic hyperthermia observed in cultures incubated with low concentration of magnetic nanoparticles and under a low intensity alternating magnetic field, in which a macroscopic temperature rise is not observed, is still not understood. In the present study, we investigate the production of intracellular Reactive Oxygen Species (ROS) as a mechanism to induce cell death under these conditions. In this study, the production and influence of ROS on the viability of HepG2 human hepatoma cells (used as a model cell line) are analyzed under the application of variable magnetic fields using hyperthermia agents, such as biomimetic magnetic nanoparticles (BMNPs) mediated by magnetosome MamC protein from Magnetococcus marinus MC-1. The results show that intracellular ROS production increases up to ∼90% following upon the exposure of AMF to HepG2 cells containing BMNPs, which could determine the loss of cell viability (up to ∼40% reduction) without a significant rise in temperature. Such ROS production is linked to mitochondrial dysfunction caused by the application of AMF to cells containing BMNPs.