Evaluation of La1−xSrxMnO3 (0 ≤ x < 0.4) synthesised via a modified sol–gel method as mediators for magnetic fluid hyperthermia

A range of lanthanum strontium manganates (La1−xSrxMnO3–LSMO) where 0 ≤ x < 0.4 were prepared using a modified peroxide sol–gel synthesis method. The magnetic nanoparticle (MNP) clusters obtained for each of the materials were characterised using scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and infra-red (IR) spectroscopy in order to confirm the crystalline phases, crystallite size and cluster morphology. The magnetic properties of the materials were assessed using the Superconducting quantum interference device (SQUID) to evaluate the magnetic susceptibility, Curie temperature (Tc) and static hysteretic losses. Induction heating experiments also provided an insight into the magnetocaloric effect for each material. The specific absorption rate (SAR) of the materials was evaluated experimentally and via numerical simulations. The magnetic properties and heating data were linked with the crystalline structure to make predictions with respect to the best LSMO composition for mild hyperthermia (41 °C ≤ T ≤ 46 °C). La0.65Sr0.35MnO3, with crystallite diameter of 82.4 nm, (agglomerate size of ∼10 μm), Tc of 89 °C and SAR of 56 W gMn−1 at a concentration 10 mg mL−1 gave the optimal induction heating results (Tmax of 46.7 °C) and was therefore deemed as most suitable for the purposes of mild hyperthermia, vide infra.

Thermal infrared image processing to assess heat generated by magnetic nanoparticles for hyperthermia applications

Magnetic fluid hyperthermia (MFH) is considered a promising therapeutic technique for the treatment of cancer cells, in which magnetic nanoparticles (MNPs) with superparamagnetic behavior generate mild-temperatures under an AC magnetic field to selectively destroy the abnormal cancer cells, in detriment of the healthy ones. However, the poor heating efficiency of most NMPs and the imprecise experimental determination of the temperature field during the treatment, are two of the majors drawbacks for its clinical advance. Thus, in this work, different MNPs were developed and tested under an AC magnetic field (~1.10 kA/m and 200 kHz), and the heat generated by them was assessed by an infrared camera. The resulting thermal images were processed in MATLAB after the thermographic calibration of the infrared camera. The results show the potential to use this thermal technique for the improvement and advance of MFH as a clinical therapy.

In vitro evaluation of combined hyperthermia and photodynamic effects using magnetoliposomes loaded with cucurbit[7]uril zinc phthalocyanine complex on melanoma

The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs) and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects while using melanoma cells (B16-F10) as model. The liposomal formulations were characterized by both average diameter and zeta potential. The vesicle average size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to 0.230. The zeta potential was significantly positive with values between 48 and 57 mV. The cell viability (CV) after PD and HT treatments was assessed by colorimetric MTI method. Melanoma cells were initially treated with the liposome formulation without light and magnetic field application, revealing cell viability not different from the control cells (p > 0.05). Photodynamic and hyperthermia assays were also applied separately, demonstrating that PD is more effective than HT in reducing the CV of the neoplastic cells. Combined application of both PD and HT treatments was even more effective in reducing the CV of B16-F10 cells. At the highest light dose (2 J/cm(2)) and under magnetic field activation the CV was about half than PD applied alone. Therefore, the use of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy (PDT) and magnetohyperthermia (MHT) application can be considered as a potential tool to treat malignant melanoma. (C) 2012 Elsevier B.V. All rights reserved.

Biocompatible Magnetic Microspheres for Use in PDT and Hyperthermia

Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MU.

In vitro cytotoxicity of Selol-loaded magnetic nanocapsules against neoplastic cell lines under AC magnetic field activation

The goals of this study are to evaluate in vitro compatibility of magnetic nanomaterials and their therapeutic potential against cancer cells. Highly stable ionic magnetic fluid sample (maghemite, gamma-Fe2O3) and Selol were incorporated into polymeric nanocapsules by nanoprecipitation method. The cytotoxic effect of Selol-loaded magnetic nanocapsules was assessed on murine melanoma (B16-F10) and oral squamous cell carcinoma (OSCC) cell lines following AC magnetic field application. The influence of different nanocapsules on cell viability was investigated by colorimetric MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the absence of AC magnetic field Selol-loaded magnetic nanocapsules, containing 100 mu g/mL Selol plus 5 x 10(12) particle/mL, showed antitumoral activity of about 50% on B16-F10 melanoma cells while OSCC carcinoma cells demonstrated drug resistance at all concentrations of Selol and magnetic fluid (range of 100-500 mu g/mL Selol and 5 x 10(12) -2.5 x 10(13) particle/mL). On the other hand, under AC applied fields (1 MHz and 40 Oe amplitude) B16-F10 cell viability was reduced down to 40.5% (+/- 3.33) at the highest concentration of nanoencapsulated Selol. The major effect, however, was observed on OSCC cells since the cell viability drops down to about 33.3% (+/- 0.38) under application of AC magnetic field. These findings clearly indicate that the Selol-loaded magnetic nanocapsules present different toxic effects on neoplastic cell lines. Further, the cytotoxic effect was maximized under AC magnetic field application on OSCC, which emphasizes the effectiveness of the magnetohyperthermia approach. (C) 2012 American Institute of Physics. [doi: 10.1063/1.3680541]

Co-nanoencapsulation of magnetic nanoparticles and selol for breast tumor treatment: in vitro evaluation of cytotoxicity and magnetohyperthermia efficacy

Antitumor activities have been described in selol, a hydrophobic mixture of molecules containing selenium in their structure, and also in maghemite magnetic nanoparticles (MNPs). Both selol and MNPs were co-encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanocapsules for therapeutic purposes. The PLGA-nanocapsules loaded with MNPs and selol were labeled MSE-NC and characterized by transmission and scanning electron microscopy, electrophoretic mobility, photon correlation spectroscopy, presenting a monodisperse profile, and positive charge. The antitumor effect of MSE-NC was evaluated using normal (MCF-10A) and neoplastic (4T1 and MCF-7) breast cell lines. Nanocapsules containing only MNPs or selol were used as control. MTT assay showed that the cytotoxicity induced by MSE-NC was dose and time dependent. Normal cells were less affected than tumor cells. Cell death occurred mainly by apoptosis. Further exposure of MSE-NC treated neoplastic breast cells to an alternating magnetic field increased the antitumor effect of MSE-NC. It was concluded that selol-loaded magnetic PLGA-nanocapsules (MSE-NC) represent an effective magnetic material platform to promote magnetohyperthermia and thus a potential system for antitumor therapy.

Platinum dendritic nanoparticles with magnetic behavior

Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.

Size Control and Magnetic Property Trends in Cobalt Ferrite Nanoparticles Synthesized Using an Aqueous Chemical Route

Cobalt ferrite (CoFe2O4) is an engineering material which is used for applications such as magnetic cores, magnetic switches, hyperthermia based tumor treatment, and as contrast agents for magnetic resonance imaging. Utility of ferrites nanoparticles hinges on its size, dispersibility in solutions, and synthetic control over its coercivity. In this work, we establish correlations between room temperature co-precipitation conditions, and these crucial materials parameters. Furthermore, post-synthesis annealing conditions are correlated with morphology, changes in crystal structure and magnetic properties. We disclose the synthesis and process conditions helpful in obtaining easily sinterable CoFe2O4 nanoparticles with coercive magnetic flux density (H-c) in the range 5.5-31.9 kA/m and M-s in the range 47.9-84.9 A.m(2)Kg(-1). At a grain size of similar to 54 +/- 2 nm (corresponding to 1073 K sintering temperature), multi-domain behavior sets in, which is indicated by a decrease in H-c. In addition, we observe an increase in lattice constant with respect to grain size, which is the inverse of what is expected of in ferrites. Our results suggest that oxygen deficiency plays a crucial role in explaining this inverse trend. We expect the method disclosed here to be a viable and scalable alternative to thermal decomposition based CoFe2O4 synthesis. The magnetic trends reported will aid in the optimization of functional CoFe2O4 nanoparticles

Synthesis and Characterization of Magnetic Composites Based on Cis-Polyisoprene and CoFe(2)O(4) Nanoparticles

CoFe(2)O(4) nanoparticles were obtained by the co-precipitation method. They were further modified by the adsorption of ricinoleic acid (RA). The non-modified and modified CoFe(2)O(4)/RA nanoparticles were characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), Raman, and Fourier transform infrared (FTIR) spectroscopy. The modified particles present a mean diameter < 20 nm. The adsorption of RA on the CoFe(2)O(4) surface is characterized by the IR absorptions of the RA while in the Raman spectrum the predominant signals are those from the CoFe(2)O(4). The cis-polyisoprene (PI) composite was prepared by dissolving PI in cyclohexane followed by the addition of a magnetic fluid based on CoFe(2)O(4)/RA nanoparticles dispersed in cyclohexane. After solvent evaporation a magnetic composite was obtained and characterized by AFM, Raman, and FTIR measurements. AFM images show uniformly CoFe(2)O(4)/RA particles distributed in the PI matrix. Raman spectra obtained for the composites reveal the characteristic Raman peaks of PI and CoFe(2)O(4) nanoparticles.

DEVELOPMENT OF AN IONIC LIQUID FERROFLUID ELECTROSPRAY SOURCE AND MODE SHAPE STUDIES OF A FERROFLUID IN A NON-UNIFORM MAGNETIC FIELD

An electrospray source has been developed using a novel new fluid that is both magnetic and conductive. Unlike conventional electrospray sources that required microfabricated structures to support the fluid to be electrosprayed, this new electrospray fluid utilizes the Rosensweig instability to create the structures in the magnetic fluid when an external magnetic field was applied. Application of an external electric field caused these magnetic fluid structures to spray. These fluid based structures were found to spray at a lower onset voltage than was predicted for electrospray sources with solid structures of similar geometry. These fluid based structures were also found to be resilient to damage, unlike the solid structures found in traditional electrospray sources. Further, experimental studies of magnetic fluids in non-uniform magnetic fields were conducted. The modes of Rosensweig instabilities have been studied in-depth when created by uniform magnetic fields, but little to no studies have been performed on Rosensweig instabilities formed due to non-uniform magnetic fields. The measured spacing of the cone-like structures of ferrofluid, in a non-uniform magnetic field, were found to agree with a proposed theoretical model.

Research lines in Hyperthermia at the Bioinstrumentation Laboratory of the Centre for Biomedical Technology

The Bioinstrumentation Laboratory belongs to the Centre for Biomedical Technology (CTB) of the Technical University of Madrid and its main objective is to provide the scientific community with devices and techniques for the characterization of micro and nanostructures and consequently finding their best biomedical applications. Hyperthermia (greek word for “overheating”) is defined as the phenomenon that occurs when a body is exposed to an energy generating source that can produce a rise in temperature (42-45ºC) for a given time [1]. Specifically, the aim of the hyperthermia methods used in The Bioinstrumentation Laboratory is the development of thermal therapies, some of these using different kinds of nanoparticles, to kill cancer cells and reduce the damage on healthy tissues. The optical hyperthermia is based on noble metal nanoparticles and laser irradiation. This kind of nanoparticles has an immense potential associated to the development of therapies for cancer on account of their Surface Plasmon Resonance (SPR) enhanced light scattering and absorption. In a short period of time, the absorbed light is converted into localized heat, so we can take advantage of these characteristics to heat up tumor cells in order to obtain the cellular death [2]. In this case, the laboratory has an optical hyperthermia device based on a continuous wave laser used to kill glioblastoma cell lines (1321N1) in the presence of gold nanorods (Figure 1a). The wavelength of the laser light is 808 nm because the penetration of the light in the tissue is deeper in the Near Infrared Region. The first optical hyperthermia results show that the laser irradiation produces cellular death in the experimental samples of glioblastoma cell lines using gold nanorods but is not able to decrease the cellular viability of cancer cells in samples without the suitable nanorods (Figure 1b) [3]. The generation of magnetic hyperthermia is performed through changes of the magnetic induction in magnetic nanoparticles (MNPs) that are embedded in viscous medium. The Figure 2 shows a schematic design of the AC induction hyperthermia device in magnetic fluids. The equipment has been manufactured at The Bioinstrumentation Laboratory. The first block implies two steps: the signal selection with frequency manipulation option from 9 KHz to 2MHz, and a linear output up to 1500W. The second block is where magnetic field is generated ( 5mm, 10 turns). Finally, the third block is a software control where the user can establish initial parameters, and also shows the temperature response of MNPs due to the magnetic field applied [4-8]. The Bioinstrumentation Laboratory in collaboration with the Mexican company MRI-DT have recently implemented a new research line on Nuclear Magnetic Resonance Hyperthermia, which is sustained on the patent US 7,423,429B2 owned by this company. This investigation is based on the use of clinical MRI equipment not only for diagnosis but for therapy [9]. This idea consists of two main facts: Magnetic Resonance Imaging can cause focal heating [10], and the differentiation in resonant frequency between healthy and cancer cells [11]. To produce only heating in cancer cells when the whole body is irradiated, it is necessary to determine the specific resonant frequency of the target, using the information contained in the spectra of the area of interest. Then, special RF pulse sequence is applied to produce fast excitation and relaxation mechanism that generates temperature increase of the tumor, causing cellular death or metabolism malfunction that stops cellular division

Horizontal deflection of single particle in a paramagnetic fluid

This paper describes the horizontal deflection behaviour of a single particle in paramagnetic fluids under a high-gradient superconducting magnetic field. A glass box was designed to carry out experiments and test assumptions. It was found that the particles were deflected away from the magnet bore centre and particles with different density and/or susceptibility settled at a certain position on the container floor due to the combined forces of gravity and magneto-Archimedes as well as lateral buoyant (displacement) force. Matlab was chosen to simulate the movement of the particle in the magnetic fluid, the simulation results were in good accordance with experimental data. The results presented here, though, are still very much in their infancy, which could potentially form the basis of a new approach to separating materials based on a combination of density and susceptibility. Graphical abstract: [Figure not available: see fulltext.] © 2014 EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.

Tailoring Magnetic, Mechanical and Dielectric Properties of Magnetorheological Elastomers based on Natural Rubber and Iron by Magnetic Field Assisted Curing for Possible Applications

If magnetism is universal in nature, magnetic materials are ubiquitous. A life without magnetism is unthinkable and a day without the influence of a magnetic material is unimaginable. They find innumerable applications in the form of many passive and active devices namely, compass, electric motor, generator, microphone, loud speaker, maglev train, magnetic resonance imaging, data recording and reading, hadron collider etc. The list is endless. Such is the influence of magnetism and magnetic materials in ones day to day life. With the advent of nanoscience and nanotechnology, along with the emergence of new areas/fields such as spintronics, multiferroics and magnetic refrigeration, the importance of magnetism is ever increasing and attracting the attention of researchers worldwide. The search for a fluid which exhibits magnetism has been on for quite some time. However nature has not bestowed us with a magnetic fluid and hence it has been the dream of many researchers to synthesize a magnetic fluid which is thought to revolutionize many applications based on magnetism. The discovery of a magnetic fluid by Jacob Rabinow in the year 1952 paved the way for a new branch of Physics/Engineering which later became magnetic fluids. This gave birth to a new class of material called magnetorheological materials. Magnetorheological materials are considered superior to electrorheological materials in that magnetorheology is a contactless operation and often inexpensive.Most of the studies in the past on magnetorheological materials were based on magnetic fluids. Recently the focus has been on the solid state analogue of magnetic fluids which are called Magnetorheological Elastomers (MREs). The very word magnetorheological elastomer implies that the rheological properties of these materials can be altered by the influence of an external applied magnetic field and this process is reversible. If the application of an external magnetic field modifies the viscosity of a magnetic fluid, the effect of external magnetic stimuli on a magnetorheological elastomer is in the modification of its stiffness. They are reversible too. Magnetorheological materials exhibit variable stiffness and find applications in adaptive structures of aerospace, automotive civil and electrical engineering applications. The major advantage of MRE is that the particles are not able to settle with time and hence there is no need of a vessel to hold it. The possibility of hazardous waste leakage is no more with a solid MRE. Moreover, the particles in a solid MRE will not affect the performance and durability of the equipment. Usually MR solids work only in the pre yield region while MR fluids, typically work in the post yield state. The application of an external magnetic field modifies the stiffness constant, shear modulus and loss modulus which are complex quantities. In viscoelastic materials a part of the input energy is stored and released during each cycle and a part is dissipated as heat. The storage modulus G′ represents the capacity of the material to store energy of deformation, which contribute to material stiffness. The loss modulusG′′ represents the ability of the material to dissipate the energy of deformation. Such materials can find applications in the form of adaptive vibration absorbers (ATVAs), stiffness tunable mounts and variable impedance surfaces. MREs are an important material for automobile giants and became the focus of this research for eventual automatic vibration control, sound isolation, brakes, clutches and suspension systems

Superparamagnetic Liposomes for MRI Monitoring and External Magnetic Field-Induced Selective Targeting of Malignant Brain Tumors

International audience

纳米水基磁性液体在肿瘤治疗领域的研究进展

结合作者在纳米磁性液体方面的研究经历，介绍了生物医学应用领域纳米磁性粒子的组成结构及特点，指出高分子改性纳米磁性粒子具有生物相容性好、稳定性强、载药量高的优点，并对目前高分子改性纳米四氧化三铁颗粒的制备方法及特点进行了对比分析。指出进一步研制磁响应性强、载药量高、粒度分布均匀的纳米磁性粒子，使之对癌细胞具有亲和作用，尽量避免对毛细血管网状内皮系统的清除，是未来肿瘤治疗领域纳米磁性粒子的研发目标，并对目前制备方法中存在的不足提出了改进的建议。