Magnetic properties of nanoparticles as a function of their spatial distribution on liposomes and cells.

The aggregation processes of magnetic nanoparticles in biosystems are analysed by comparing the magnetic properties of three systems with different spatial distributions of the nanoparticles. The first one is iron oxide nanoparticles (NPs) of 14 nm synthesized by coprecipitation with two coatings, (3-aminopropyl)trimethoxysilane (APS) and dimercaptosuccinic acid (DMSA). The second one is liposomes with encapsulated nanoparticles, which have different configurations depending on the NP coating (NPs attached to the liposome surface or encapsulated in its aqueous volume). The last system consists of two cell lines (Pan02 and Jurkat) incubated with the NPs. Dynamic magnetic behaviour (AC) was analysed in liquid samples, maintaining their colloidal properties, while quasi-static (DC) magnetic measurements were performed on lyophilised samples. AC measurements provide a direct method for determining the effect of the environment on the magnetization relaxation of nanoparticles. Thus, the imaginary (χ'') component shifts to lower frequencies as the aggregation state increases from free nanoparticles to those attached or embedded into liposomes in cell culture media and more pronounced when internalized by the cells. DC magnetization curves show no degradation of the NPs after interaction with biosystems in the analysed timescale. However, the blocking temperature is shifted to higher temperatures for the nanoparticles in contact with the cells, regardless of the location, the incubation time, the cell line and the nanoparticle coating, supporting AC susceptibility data. These results indicate that the simple fact of being in contact with the cells makes the nanoparticles aggregate in a non-controlled way, which is not the same kind of aggregation caused by the contact with the cell medium nor inside liposomes.

Anisotropic magnetic nanoparticles for biomedicine: bridging frequency separated AC-field controlled domains of actuation.

Magnetic nanoparticles (MNPs) constitute promising nanomedicine tools based on the possibility of obtaining different actuations (for example, heating or mechanical response) triggered by safe remote stimuli. Particularly, the possibility of performing different tasks using the same entity constitutes a main research target towards optimizing the treatment. But such a goal represents, in general, a very difficult step because the requisites for achieving efficient responses for separate actuations are often disparate - if not completely incompatible. An example of this is the response of MNPs to external AC fields, which could in principle be exploited for either magneto-mechanical actuation (MMA) at low frequencies (tens of Hz); or heat release at high frequency (0.1-1 MHz range) for magnetic fluid hyperthermia (MFH). The problem is that efficient MMA involves large torque, the required material parameters for which are detrimental to high heating, thus hindering the possibility of effective alternation between both responses. To overcome such apparent incompatibility, we propose a simple approach based on the use of anisotropic MNPs. The key idea is that the AC-frequency change must be concurrent with a field-amplitude variation able to promote - or impede - the reversal over the shape-determined anisotropy energy barrier. This way it is possible to switch the particle response between an efficient (magnetically dissipationless) rotation regime at low-f, for MMA, and a "frozen" (non-rotatable) high-energy-dissipation regime at high-f, for MFH. Furthermore, we show that such an alternation can also be achieved within the same high-f MFH regime. We use combined Brownian dynamics and micromagnetic simulations, based on real experimental samples, to show how such a field threshold can be tuned to working conditions with hexagonal-disk shape anisotropy.

Oriented Attachment of Recombinant Proteins to Agarose-Coated Magnetic Nanoparticles by Means of a ß-Trefoil Lectin Domain.

Design of generic methods aimed at the oriented attachment of proteins at the interfacial environment of magnetic nanoparticles currently represents an active field of research. With this in mind, we have prepared and characterized agarose-coated maghemite nanoparticles to set up a platform for the attachment of recombinant proteins fused to the ß-trefoil lectin domain LSL150, a small protein that combines fusion tag properties with agarose-binding capacity. Analysis of the agarose-coated nanoparticles by dynamic light scattering, Fourier transform infrared spectroscopy, and thermogravimetric studies shows that decoupling particle formation from agarose coating provides better results in terms of coating efficiency and particle size distribution. LSL150 interacts with these agarose-coated nanoparticles exclusively through the recognition of the sugars of the polymer, forming highly stable complexes, which in turn can be dissociated ad hoc with the competing sugar lactose. Characterization of the complexes formed with the fusion proteins LSL-EGFP (LSL-tagged enhanced green fluorescent protein from Aquorea victoria) and LSL-BTL2 (LSL-tagged lipase from Geobacillus thermocatenolatus) provided evidence supporting a topologically oriented binding of these molecules to the interface of the agarose-coated nanoparticles. This is consistent with the marked polarity of the ß-trefoil structure where the sugar-binding sites and the N- and C-terminus ends are at opposed sides. In summary, LSL150 displays topological and functional features expected from a generic molecular adaptor for the oriented attachment of proteins at the interface of agarose-coated nanoparticles.

Effect of Nanoclustering and Dipolar Interactions in Heat Generation for Magnetic Hyperthermia.

Biomedical magnetic colloids commonly used in magnetic hyperthermia experiments often display a bidisperse structure, i.e., are composed of stable nanoclusters coexisting with well-dispersed nanoparticles. However, the influence of nanoclusters in the optimization of colloids for heat dissipation is usually excluded. In this work, bidisperse colloids are used to analyze the effect of nanoclustering and long-range magnetic dipolar interaction on the magnetic hyperthermia efficiency. Two kinds of colloids, composed of magnetite cores with mean sizes of around 10 and 18 nm, coated with oleic acid and dispersed in hexane, and coated with meso-2,3-dimercaptosuccinic acid and dispersed in water, were analyzed. Small-angle X-ray scattering was applied to thoroughly characterize nanoparticle structuring. We proved that the magnetic hyperthermia performances of nanoclusters and single nanoparticles are distinctive. Nanoclustering acts to reduce the specific heating efficiency whereas a peak against concentration appears for the well-dispersed component. Our experiments show that the heating efficiency of a magnetic colloid can increase or decrease when dipolar interactions increase and that the colloid concentration, i.e., dipolar interaction, can be used to improve magnetic hyperthermia. We have proven that the power dissipated by an ensemble of dispersed magnetic nanoparticles becomes a nonextensive property as a direct consequence of the long-range nature of dipolar interactions. This knowledge is a key point in selecting the correct dose that has to be injected to achieve the desired outcome in intracellular magnetic hyperthermia therapy.

Tuning the magnetic properties of Co-ferrite nanoparticles through the 1,2-hexadecanediol concentration in the reaction mixture.

This work reports on the effect of the 1,2-hexadecanediol content on the structural and magnetic properties of CoFe2O4 nanoparticles synthesized by thermal decomposition of metal-organic precursors in 1-octadecene. Although pseudo-spherical particles having an average size of about 8 nm and similar stoichiometry have been observed in all studied samples, a high level of variability in the crystal quality and, in turn, in the magnetic properties has been found as a function of the amount of 1,2-hexadecanediol added to the reaction mixture. The magnetic study reveals that samples progress from glassy magnetic behavior to bulk-like, ferrimagnetic order as the crystal quality improves. The analysis of the reaction mixtures by Fourier transform infrared spectroscopy at various stages of the reaction shows the key role of the 1,2-hexadecanediol in favoring the decomposition of the metal-organic precursor, formation of an intermediate Co(2+)Fe(3+)-oleate complex and, finally, the nucleation of nanoparticles at lower temperatures.

Incidence of the Brownian Relaxation Process on the Magnetic Properties of Ferrofluids.

Ferrofluids containing magnetic nanoparticles represent a special class of magnetic materials due to the added freedom of particle tumbling in the fluids. We studied this process, known as Brownian relaxation, and its effect on the magnetic properties of ferrofluids with controlled magnetite nanoparticle sizes. For small nanoparticles (below 10 nm diameter), the Néel process is expected to dominate the magnetic response, whereas for larger particles, Brownian relaxation becomes important. Temperature- and magnetic-field-dependent magnetization studies, differential scanning calorimetry, and AC susceptibility measurements were carried out for 6 and 13.5 nm diameter magnetite nanoparticles suspended in water. We identify clear fingerprints of Brownian relaxation for the sample of large-diameter nanoparticles as both magnetic and thermal hysteresis develop at the water freezing temperature, whereas the samples of small-diameter nanoparticles remain hysteresis-free down to the magnetic blocking temperature. This is supported by the temperature-dependent AC susceptibility measurements: above 273 K, the data show a low-frequency Debye peak, which is characteristic of Brownian relaxation. This peak vanishes below 273 K.

Mn-ferrite nanoparticles as promising magnetic tags for radiofrequency inductive detection and quantification in lateral flow assays.

Lateral flow assays are low-cost point-of-care devices that are stable, easy to use, and provide quick results. They are mostly used as qualitative screening tests to detect biomarkers for several diseases. Quantification of the biomarkers is sometimes desirable but challenging to achieve. Magnetic nanoparticles can be used as tags, providing both visual and magnetic signals that can be detected and quantified by magnetic sensors. In the present work, we synthesized superparamagnetic MnFe2O4 nanoparticles using the hydrothermal coprecipitation route. MnFe2O4 presents low magnetic anisotropy and high saturation magnetization, resulting in larger initial magnetic susceptibility, which is crucial for optimizing the signal in inductive sensors. We functionalized the coprecipitated nanoparticles with citric acid to achieve colloidal stability in a neutral pH and to provide carboxyl groups to their surface to bioconjugate with biomolecules, such as proteins and antibodies. The nanomaterials were characterized by several techniques, and we correlated their magnetic properties with their sensitivity and resolution for magnetic detection in radiofrequency inductive sensors. We considered the NeutrAvidin/biotin model of biorecognition to explore their potential as magnetic labels in lateral flow assays. Our results show that MnFe2O4 nanoparticles are more sensitive to inductive detection than magnetite nanoparticles, the most used nanotags in magnetic lateral flow assays. These nanoparticles present high potential as magnetic tags for the development of sensitive lateral flow immunoassays for detecting and quantifying biomarkers.

Hybrid hydrogels support neural cell culture development under magnetic actuation at high frequency.

The combination of hydrogels and magnetic nanoparticles, scarcely explored to date, offers a wide range of possibilities for innovative therapies. Herein, we have designed hybrid 3D matrices integrating natural polymers, such as collagen, chitosan (CHI) and hyaluronic acid (HA), to provide soft and flexible 3D networks mimicking the extracellular matrix of natural tissues, and iron oxide nanoparticles (IONPs) that deliver localized heat when exposed to an alternating magnetic field (AMF). First, colloidally stable nanoparticles with a hydrodynamic radius of ∼20 nm were synthesized and coated with either CHI (NPCHI) or HA (NPHA). Then, collagen hydrogels were homogeneously loaded with these coated-IONPs resulting in soft (E0 ∼ 2.6 kPa), biodegradable and magnetically responsive matrices. Polymer-coated IONPs in suspension preserved primary neural cell viability and neural differentiation even at the highest dose (0.1 mg Fe/mL), regardless of the coating, even boosting neuronal interconnectivity at lower doses. Magnetic hydrogels maintained high neural cell viability and sustained the formation of highly interconnected and differentiated neuronal networks. Interestingly, those hydrogels loaded with the highest dose of NPHA (0.25 mgFe/mg polymer) significantly impaired non-neuronal differentiation with respect to those with NPCHI. When evaluated under AMF, cell viability slightly diminished in comparison with control hydrogels magnetically stimulated, but not compared to their counterparts without stimulation. Neuronal differentiation under AMF was only affected on collagen hydrogels with the highest dose of NPHA, while non-neuronal differentiation regained control values. Taken together, NPCHI-loaded hydrogels displayed a superior performance, maybe benefited from their higher nanomechanical fluidity. STATEMENT OF SIGNIFICANCE: Hydrogels and magnetic nanoparticles are undoubtedly useful biomaterials for biomedical applications. Nonetheless, the combination of both has been scarcely explored to date. In this study, we have designed hybrid 3D matrices integrating both components as promising magnetically responsive platforms for neural therapeutics. The resulting collagen scaffolds were soft (E0 ∼ 2.6 kPa) and biodegradable hydrogels with capacity to respond to external magnetic stimuli. Primary neural cells proved to grow on these substrates, preserving high viability and neuronal differentiation percentages even under the application of a high-frequency alternating magnetic field. Importantly, those hydrogels loaded with chitosan-coated iron oxide nanoparticles displayed a superior performance, likely related to their higher nanomechanical fluidity.

Relationship between physico-chemical properties of magnetic fluids and their heating capacity.

The final goal in magnetic hyperthermia research is to use nanoparticles in the form of a colloidal suspension injected into human beings for a therapeutic application. Therefore the challenge is not only to develop magnetic nanoparticles with good heating capacities, but also with good colloidal properties, long blood circulation time and with grafted ligands able to facilitate their specific internalisation in tumour cells. Significant advances have been achieved optimising the properties of the magnetic nanoparticles, showing extremely large specific absorption rate values that will contribute to a reduction in the concentration of the magnetic fluid that needs to be administered. In this review we show the effect of different characteristics of the magnetic particles, such as size, size distribution and shape, and the colloidal properties of their aqueous suspensions, such as hydrodynamic size and surface modification, on the heating capacity of the magnetic colloids.

Inductive Heating Enhances Ripening in the Aqueous Synthesis of Magnetic Nanoparticles.

The search for competitive processes and products using environmentally friendly chemistry is, nowadays, one of the greatest challenges in materials science. In this work, we explore the influence of magnetic inductive heating on the synthesis of magnetic iron oxide nanoparticles in water, either by the coprecipitation of iron(II) and iron(III) salts or by the oxidative precipitation of an iron(II) salt. In the first case, the way the heat is transmitted to the system influences mainly the nanoparticle growth that is thermally activated reaching nanoparticles up to 16 nm. In the second case, it influences magnetic nanoparticle nucleation through the dissolution of the initial iron oxyhydroxide formed (the Green Rust) and the crystallization of magnetic iron oxide leading to nanoparticles up to 55-64 nm. This nonconventional heating method can produce monodisperse populations (size distribution <25%) of bigger magnetic iron oxide nanoparticles if the appropriate magnetic field conditions are used. The results were interpreted as an enhancement of the oriented attachment growth mechanism by the use of inductive heating, and suggest the possibility of increasing the size range of nanomaterials that can be obtained by sustainable aqueous routes using nonconventional heating, while maintaining low size dispersity.

Cubic Mesocrystal Magnetic Iron Oxide Nanoparticle Formation by Oriented Aggregation of Cubes in Organic Media: A Rational Design to Enhance the Magnetic Hyperthermia Efficiency.

Magnetic iron oxide mesocrystals have been reported to exhibit collective magnetic properties and consequently enhanced heating capabilities under alternating magnetic fields. However, there is no universal mechanism to fully explain the formation pathway that determines the particle diameter, crystal size, and shape of these mesocrystals and their evolution along with the reaction. In this work, we have analyzed the formation of cubic magnetic iron oxide mesocrystals by thermal decomposition in organic media. We have observed that a nonclassical pathway leads to mesocrystals via the attachment of crystallographically aligned primary cubic particles and grows through sintering with time to achieve a sizable single crystal. In this case, the solvent 1-octadecene and the surfactant agent biphenyl-4-carboxylic acid seem to be the key parameters to form cubic mesocrystals as intermediates of the reaction in the presence of oleic acid. Interestingly, the magnetic properties and hyperthermia efficiency of the aqueous suspensions strongly depend on the degree of aggregation of the cores forming the final particle. The highest saturation magnetization and specific absorption rate values were found for the less aggregated mesocrystals. Thus, these cubic magnetic iron oxide mesocrystals stand out as an excellent alternative for biomedical applications with their enhanced magnetic properties.

Microwave-assisted NixFe1-x nanoclusters ultra-stable to oxidation in aqueous media.

Metal alloy nanoparticles, and, in particular, permalloy, still hold an untapped potential in nanotechnology, although their poor stability against oxidation due to environmental exposure limits their use in many technological applications, and even more in life sciences. We propose a scalable single-step microwave-assisted method to produce water suspensions of Ni1-xFex nanoparticles without the need for an inert atmosphere, either organic solvents or any type of post-processing. We use hydrazine as a reducer, iron(II), iron(III) and nickel(II) chloride as precursors, 1,12-dodecanediol as a surfactant and water as a reaction medium. The mixture is heated at 160 °C for 10 minutes to obtain uniform alloy nanoparticles with sizes of around 24.5 nm for Ni (0% Fe) and 5.5 nm for 35% Fe that are forming uniform aggregates with sizes between 200 nm for Ni and 65 nm for iron oxide NPs. A linear increase of saturation magnetization is observed with an Fe content of up to 25%, whereas for larger percentages a sudden drop takes place due to the formation of iron oxides. X-ray diffraction measurements rule out the formation of any oxides after more than one year of storage at 4 °C, surely due to the presence of 1,12-dodecanediol at the surface, as evidenced by infrared spectroscopy.

Tailoring the Magnetic and Structural Properties of Manganese/Zinc Doped Iron Oxide Nanoparticles through Microwaves-Assisted Polyol Synthesis.

Tuning the fundamental properties of iron oxide magnetic nanoparticles (MNPs) according to the required biomedical application is an unsolved challenge, as the MNPs' properties are affected by their composition, their size, the synthesis process, and so on. In this work, we studied the effect of zinc and manganese doping on the magnetic and structural properties of MNPs synthesized by the microwave-assisted polyol process, using diethylene glycol (DEG) and tetraethylene glycol (TEG) as polyols. The detailed morpho-structural and magnetic characterization showed a correspondence between the higher amounts of Mn and smaller crystal sizes of the MNPs. Such size reduction was compensated by an increase in the global magnetic moment so that it resulted in an increase of the saturation magnetization. Saturation magnetization MS values up to 91.5 emu/g and NMR transverse relaxivities r2 of 294 s-1mM-1 were obtained for Zn and Mn- doped ferrites having diameters around 10 nm, whereas Zn ferrites with diameters around 15 nm reached values of MS∼ 97.2 emu/g and of r2∼ 467 s-1mM-1, respectively. Both kinds of nanoparticles were synthesized by a simple, reproducible, and more sustainable method that makes them very interesting for diagnostic applications as MRI contrast agents.

Superparamagnetic Iron Oxide Nanoparticles Decorated Mesoporous Silica Nanosystem for Combined Antibiofilm Therapy.

A crucial challenge to face in the treatment of biofilm-associated infection is the ability of bacteria to develop resistance to traditional antimicrobial therapies based on the administration of antibiotics alone. This study aims to apply magnetic hyperthermia together with controlled antibiotic delivery from a unique magnetic-responsive nanocarrier for a combination therapy against biofilm. The design of the nanosystem is based on antibiotic-loaded mesoporous silica nanoparticles (MSNs) externally functionalized with a thermo-responsive polymer capping layer, and decorated in the outermost surface with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are able to generate heat upon application of an alternating magnetic field (AMF), reaching the temperature needed to induce a change in the polymer conformation from linear to globular, therefore triggering pore uncapping and the antibiotic cargo release. The microbiological assays indicated that exposure of E. coli biofilms to 200 µg/mL of the nanosystem and the application of an AMF (202 kHz, 30 mT) decreased the number of viable bacteria by 4 log10 units compared with the control. The results of the present study show that combined hyperthermia and antibiotic treatment is a promising approach for the effective management of biofilm-associated infections.

Superparamagnetic-blocked state transition under alternating magnetic fields: towards determining the magnetic anisotropy in magnetic suspensions.

The potential of magnetic nanoparticles for acting as efficient catalysts, imaging tracers or heating mediators relays on their superparamagnetic behaviour under alternating magnetic fields. In spite of the relevance of this magnetic phenomenon, the identification of specific fingerprints to unequivocally assign superparamagnetic behaviour to nanomaterials is still lacking. Herein, we report on novel experimental and theoretical evidences related to the superparamagnetism observed in magnetic iron oxide nanoparticle suspensions at room temperature. AC magnetization measurements in a broad field frequency range from mHz to kHz and field intensities up to 40 kA m-1 unambiguously demonstrate the transition from superparamagnetic to blocked states at room temperature. Our experimental observations are supported by a theoretical model based on the stochastic Landau-Liftshitz-Gilbert equation. An empirical expression is proposed to determine the effective magnetic anisotropy from the field frequency value beyond which AC magnetization shows hysteretic behaviour. Our results significantly improve the understanding and description of the superparamagnetism of iron oxide nanoparticles, paving the way towards a more efficient exploitation of their unique magnetic properties.

Unravelling an amine-regulated crystallization crossover to prove single/multicore effects on the biomedical and environmental catalytic activity of magnetic iron oxide colloids.

Elucidation of reaction mechanisms in forming nanostructures is relevant to obtain robust and affordable protocols that can lead to materials with enhanced properties and good reproducibility. Here, the formation of magnetic iron oxide monocrystalline nanoflowers in polyol solvents using N-methyldiethanolamine (NMDEA) as co-solvent has been shown to occur through a non-classical crystallization pathway. This pathway involves intermediate mesocrystals that, in addition, can be transformed into large single colloidal nanocrystals. Interestingly, the crossover of a non-classical crystallization pathway to a classical crystallization pathway can be induced by merely changing the NMDEA concentration. The key is the stability of a green rust-like intermediate complex that modulates the nucleation rate and growth of magnetite nanocrystals. The crossover separates two crystallization domains (classical and non-classical) and three basic configurations (mesocrystals, large and small colloidal nanocrystals). The above finding facilitated the synthesis of magnetic materials with different configurations to suit various engineering applications. Consequently, the effect of the single and multicore configurations of magnetic iron oxide on the biomedical (magnetic hyperthermia and enzyme immobilization) and catalytic activity (Fenton-like reactions and photo-Fenton-like processes driven by visible light irradiation) has been experimentally demonstrated.

Understanding MNPs Behaviour in Response to AMF in Biological Milieus and the Effects at the Cellular Level: Implications for a Rational Design That Drives Magnetic Hyperthermia Therapy toward Clinical Implementation.

Hyperthermia has emerged as a promising alternative to conventional cancer therapies and in fact, traditional hyperthermia is now commonly used in combination with chemotherapy or surgery during cancer treatment. Nevertheless, non-specific application of hyperthermia generates various undesirable side-effects, such that nano-magnetic hyperthermia has arisen a possible solution to this problem. This technique to induce hyperthermia is based on the intrinsic capacity of magnetic nanoparticles to accumulate in a given target area and to respond to alternating magnetic fields (AMFs) by releasing heat, based on different principles of physics. Unfortunately, the clinical implementation of nano-magnetic hyperthermia has not been fluid and few clinical trials have been carried out. In this review, we want to demonstrate the need for more systematic and basic research in this area, as many of the sub-cellular and molecular mechanisms associated with this approach remain unclear. As such, we shall consider here the biological effects that occur and why this theoretically well-designed nano-system fails in physiological conditions. Moreover, we will offer some guidelines that may help establish successful strategies through the rational design of magnetic nanoparticles for magnetic hyperthermia.

Engineering Iron Oxide Nanocatalysts by a Microwave-Assisted Polyol Method for the Magnetically Induced Degradation of Organic Pollutants.

Advanced oxidation processes constitute a promising alternative for the treatment of wastewater containing organic pollutants. Still, the lack of cost-effective processes has hampered the widespread use of these methodologies. Iron oxide magnetic nanoparticles stand as a great alternative since they can be engineered by different reproducible and scalable methods. The present study consists of the synthesis of single-core and multicore magnetic iron oxide nanoparticles by the microwave-assisted polyol method and their use as self-heating catalysts for the degradation of an anionic (acid orange 8) and a cationic dye (methylene blue). Decolorization of these dyes was successfully improved by subjecting the catalyst to an alternating magnetic field (AMF, 16 kA/m, 200 kHz). The sudden temperature increase at the surface of the catalyst led to an intensification of 10% in the decolorization yields using 1 g/L of catalyst, 0.3 M H2O2 and 500 ppm of dye. Full decolorization was achieved at 90 °C, but iron leaching (40 ppm) was detected at this temperature leading to a homogeneous Fenton process. Multicore nanoparticles showed higher degradation rates and 100% efficiencies in four reusability cycles under the AMF. The improvement of this process with AMF is a step forward into more sustainable remediation techniques.

Combined Magnetoliposome Formation and Drug Loading in One Step for Efficient Alternating Current-Magnetic Field Remote-Controlled Drug Release.

We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NPs) with negative, positive, and hydrophobic surfaces that were incorporated outside, inside, or between the lipid bilayers, respectively. To characterize how NPs are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NPs are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 °C with high enthalpy 34.8 J/g) avoiding the leakage of the encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100% of cellular uptake was achieved with a high cell survival (above 80%), which is preserved (83%) for doxorubicin-loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 h, leading to a cell survival reduction of 20%. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating to avoid drug degradation. In conclusion, these drug-loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place, efficiently using an external AMF to reduce or even eliminate side effects.

The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells.

The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was detected in cells incubated with neutral charged nanoparticles, while negative particles showed different behaviour depending on the nature of the coating. Thus, dimercaptosuccinic-coated nanoparticles showed low cellular uptake with non-toxic effects, while heparin-coated particles showed cellular uptake only at high nanoparticle concentrations and induced abnormal mitotic spindle configurations. Finally, cationic magnetic nanoparticles show excellent properties for possible in vivo biomedical applications such as cell tracking by magnetic resonance imaging (MRI) and cancer treatment by hyperthermia: (i) they enter into cells with high effectiveness, and are localized in endosomes; (ii) they can be easily detected inside cells by optical microscopy, (iii) they are retained for relatively long periods of time, and (iv) they do not induce any cytotoxicity.