The importance of cell uptake in photothermal treatments mediated by biomimetic magnetic nanoparticles.

Biomimetic magnetic nanoparticles (BMNPs) mediated by MamC have proven to be photothermal agents able to allow an optimized cytotoxicity against tumoral cells when used simultaneously as drug nanotransporters and as hyperthermia agents. However, it remains unclear whether BMNPs need to be internalized by the cells and/or if there is a threshold for internal Fe concentration for the photothermal therapy to be effective. In this study, three different situations for photothermal treatments have been simulated to disentangle the effect of BMNPs cell uptake on cell viability after photothermal treatments. Human hepatoblastoma (HepG2) cell line was treated with suspensions of BMNPs, and protocols were developed to have only intracellular BMNPs, only extracellular BMNPs or both, followed by photothermal exposure of the treated cell cultures. Our data demonstrate that: (1) Although the heating efficiency of the photothermal agent is not altered by its location (intra/extracellular), the intracellular location of BMNPs is crucial to ensure the cytotoxic effect of photothermal treatments, especially at low Fe concentration. In fact, the concentration of BMNPs needed to reach the same cytotoxic effect following upon laser irradiation of 0.2 W/cm2 is three times larger if BMNPs are located extracellularly compared to that needed if BMNPs are located intracellularly; (2) For a given location of the BMNPs, cell death increases with BMNPs (or Fe) concentration. When BMNPs are located intracellularly, there is a threshold for Fe concentration (∼ 0.5 mM at laser power intensities of 0.1 W/cm2) needed to affect cell viability following upon cell exposure to photothermia. (3) Bulk temperature rise is not the only factor accounting for cell death. Actually, temperature increases inside the cells cause more damage to cell structures and trigger cell death more efficiently than an increase in the temperature outside the cell.

Antibacterial directed chemotherapy using AS-48 peptide immobilized on biomimetic magnetic nanoparticles combined with magnetic hyperthermia.

The design of new strategies to increase the effectiveness of the antibacterial treatments is a main goal in public health. So, the aim of the study was to achieve a local antibacterial directed therapy as novel alternative allowing both, the delivery of the drug at the target, while minimizing undesirable side effects, thus anticipating an enhanced effectiveness. Hence, we have developed an innovative nanoformulation composed by biomimetic magnetic nanoparticles functionalized with the antimicrobial peptide AS-48 and its potential against Gram-positive and Gram-negative bacteria, either by itself or combined with magnetic hyperthermia has been investigated. Besides, the physical properties, binding efficiency, stability and mechanism of action of this nanoassembly are analyzed. Remarkably, the nanoassembly has a strong bactericidal effect on Gram-positive bacteria, but surprisingly also on E. coli and, finally, when combined with magnetic hyperthermia, on P. aeruginosa and K. pneumoniae. The results obtained represent a breakthrough since it allows a local treatment of infections, reducing and concentrating the dose of antimicrobial compounds, avoiding secondary effects, including the resistance generation and particularly because the combination with magnetic hyperthermia helps sensitizing resistant bacteria to the bactericidal effect of AS-48. Thus, this new formulation should be considered a promising tool in the antibacterial fight.

Hyperthermia-Triggered Gemcitabine Release from Polymer-Coated Magnetite Nanoparticles.

In this work a combined, multifunctional platform, which was devised for the simultaneous application of magnetic hyperthermia and the delivery of the antitumor drug gemcitabine, is described and tested in vitro. The system consists of magnetite particles embedded in a polymer envelope, designed to make them biocompatible, thanks to the presence of poly (ethylene glycol) in the polymer shell. The commercial particles, after thorough cleaning, are provided with carboxyl terminal groups, so that at physiological pH they present negative surface charge. This was proved by electrophoresis, and makes it possible to electrostatically adsorb gemcitabine hydrochloride, which is the active drug of the resulting nanostructure. Both electrophoresis and infrared spectroscopy are used to confirm the adsorption of the drug. The gemcitabine-loaded particles are tested regarding their ability to release it while heating the surroundings by magnetic hyperthermia, in principle their chances as antitumor agents. The release, with first-order kinetics, is found to be faster when carried out in a thermostated bath at 43 °C than at 37 °C, as expected. But, the main result of this investigation is that while the particles retain their hyperthermia response, with reasonably high heating power, they release the drug faster and with zeroth-order kinetics when they are maintained at 43 °C under the action of the alternating magnetic field used for hyperthermia.

Magnetic Nanoparticles Coated with a Thermosensitive Polymer with Hyperthermia Properties.

Magnetic nanoparticles (MNPs) have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by the enhanced permeability and retention effect. Their incorporation into biopolymer coatings enables the preparation of magnetic field-responsive, biocompatible nanoparticles that are well dispersed in aqueous media. Here we describe a synthetic route to prepare functionalized, stable magnetite nanoparticles (MNPs) coated with a temperature-responsive polymer, by means of the hydrothermal method combined with an oil/water (o/w) emulsion process. The effects of both pH and temperature on the electrophoretic mobility and surface charge of these MNPs are investigated. The magnetite/polymer composition of these systems is detected by Fourier Transform Infrared Spectroscopy (FTIR) and quantified by thermogravimetric analysis. The therapeutic possibilities of the designed nanostructures as effective heating agents for magnetic hyperthermia are demonstrated, and specific absorption rates as high as 150 W/g, with 20 mT magnetic field and 205 kHz frequency, are obtained. This magnetic heating response could provide a promising nanoparticle system for combined diagnostics and cancer therapy.

Dynamic characterization of extremely bidisperse magnetorheological fluids.

In this work, we investigate the stability and redispersibility of magnetorheological fluids (MRFs). These are disperse systems where the solid is constituted by ferro- or ferri-magnetic microparticles. Upon the application of external magnetic field, they experience rapid and reversible increases in yield stress and viscosity. The problem considered here is first of all the determination of their stability against sedimentation, an essential issue in their practical application. Although this problem is typically faced through the addition of thixotropic agents to the liquid medium, in this work, we propose the investigation of the effect of magnetic nanoparticles addition, so that the dispersion medium is in reality a ferrofluid. It is found that a volume fraction of nanoparticles not higher than 3% is enough to provide a long-lasting stabilization to MRFs containing above 30% iron microparticles. In the, in fact unavoidable, event of settling, the important point is the ease of redispersion of the sediment. This is indirectly evaluated in the present investigation by measuring the penetration force in the suspension, using a standard hardness needle. Again, it is found that the nanoparticles addition produces soft sediments by avoiding short-range attractions between the large iron particles. Finally, the performance of the designed MRFs is evaluated by obtaining their steady-state rheograms for different volume fractions of magnetite and different magnetic field strengths. The yield stress is found to be strongly field-dependent, and it can achieve the high values expected in standard magnetorheological fluids but with improved stability and redispersibility.

Description and performance of a fully automatic device for the study of the sedimentation of magnetic suspensions.

In this paper we describe an experimental setup for the automatic determination of the sedimentation behavior of magnetic suspensions (i.e., disperse systems consisting on ferro- or ferri-magnetic particles in a suitable fluid) of arbitrary volume fraction of solids. The device is based on the evaluation of the inductance of a thin coil surrounding the test tube containing the sample. The inductance L is evaluated from the measurement of the resonant frequency of a parallel LC circuit constructed with the coil and a capacitor of known capacitance. The coil can be moved vertically along the tube at specified steps and time intervals, and from the knowledge of L as a function of the vertical position and time, one can get an image of the particle concentration profiles at given instants of time. The performance of the device is tested against suspensions of spherical iron particles in the micrometer size range dispersed in silicone oil, with various initial concentrations of solids. The sedimentation profiles are then compared with the predictions of existing models for the settling of disperse systems of non-interacting particles.

Adsorption of anionic and cationic surfactants on anionic colloids: supercharging and destabilization.

We present herein a study on the adsorption of anionic (SDS), cationic (CTAB), and nonionic (C(12)E(5)) surfactants onto anionic silica nanoparticles. The effects of this adsorption are studied by means of the static structure factor, S(q), and the collective diffusion coefficient, D(c), obtained from small-angle X-ray scattering and dynamic light scattering measurements, respectively. The effective charge on the particles was determined also from classical electrophoresis and electroacoustic sonic-amplitude measurements. The surface tension of the sample was also investigated. Of particular note is the adsorption of SDS onto the silica nanoparticles, which leads to supercharging of the interface. This has interesting repercussions for structures obtained by the layer-by-layer (LbL) technique, because emulsions stabilized with supercharged and hydrophobized silica are perfect candidates for use in a multilayer system.

An experimental method for the measurement of the stability of concentrated magnetic fluids.

In this paper we present a device and method suited to the experimental determination of the sedimentation rate of concentrated suspensions of magnetic particles. The method is based on the measurement of the inductance of one or more sensing coils located at specified positions around a test tube containing the suspension. Such measurement is made possible by the determination of the resonant frequency of a parallel LC circuit in which L is the inductance of the sensing coil and C is the capacity of a capacitor chosen in such a way that the resonant frequency is easily measured. Upon calibration it is possible to relate the resonant frequency to the volume fraction of the particles at the coil location. The method is applied in the present work to the evaluation of the sedimentation kinetics of iron suspensions in base fluids of viscosities ranging from 0.3 to 100 mPa s and volume fractions of solids between 2.5 and 25%. Both if a single coil is used and if a set of three coils at different positions are employed, it is possible to detect the rate of accumulation of particles at the bottom of the container as well as a phenomenon of buoyancy of the largest particles brought about by the hydrostatic push of a dense fluid consisting of the smallest particles in the supporting liquid.