Magnetic and hydrogel composite materials for hyperthermia applications

Micron-sized magnetic particles (Fe3O4) were dispersed in a polyvinyl alcohol hydrogel to study their potential for hyperthermia applications. Heating characteristics of this ferrogel in an alternating magnetic field (375 kHz) were investigated. The results indicate that the amount of heat generated depends on the Fe3O4 content and magnetic field amplitude. A stable maximum temperature ranging from 43 to 47 degrees C was successfully achieved within 5-6 min. The maximum temperature was a function of Fe3O4 concentration. A specific absorption rate of up to 8.7 W/g Fe3O4 was achieved; this value was found to depend on the magnetic field strength. Hysteresis loss is the main contribution to the heating effect experienced by the sample.     

PNIPA/PEG多孔智能水凝胶的辐射合成与性能研究

采用辐射法合成了一系列具有合适相变温度和快速响应性能的PNIPA/PEG多孔智能水凝胶,用红外光谱分析了水凝胶的结构,并测定了水凝胶的溶胀动力学、平衡溶胀率和退溶胀动力学,研究了辐射剂量和成孔剂分子量对凝胶性能的影响.结果表明,PEG分子仅在聚合交联过程中充当成孔剂,不参与反应,反应后被除去;PNIPA/PEG水凝胶的平衡溶胀率(SR)随辐射剂量的升高而减小,其最低临界相转变温度(LCST)在37℃左右,且基本不受辐射剂量的影响;溶胀性能随着PEG分子量的增大而提高.     

A cylindrical-section ultrasound phased-array applicator for hyperthermia cancer therapy

A phased-array applicator geometry for deep localized hyperthermia is presented. The array consists of rectangular transducer elements forming a section of a cylinder that conforms to the body portals in the abdominal and pelvic regions. Focusing and scanning properties of the cylindrical-section array are investigated in homogeneous lossy media using appropriate computer simulations. The characteristic focus of this array is shown to be spatially limited in both transverse and longitudinal directions with intensity gain values suitable for deep hyperthermia applications. The ability of the cylindrical-section phased array to generate multiple foci using the field conjugation method is examined. The effect of the grating lobes on the power deposition pattern of the scanned field is shown to be minimal. Steady-state temperature distributions are simulated using a three-dimensional thermal model of the normal tissue layers surrounding a tumor of typical volume. The advantages and the limitations of this array configuration are discussed.     

Localised heating of tumours utilising injectable magnetic nanoparticles for hyperthermia cancer therapy

This study reports an investigation of hyperthermia cancer therapy utilising an alternating magnetic field to induce a localised temperature increase on tumours by using injectable magnetic nanoparticles. In-vitro and in-vivo experiments represent the feasibility of hyperthermia cancer therapy. A feedback temperature control system was first developed to keep the nanoparticles at a constant temperature to prevent overheating in the tumours such that a safer and more precise cancer therapy becomes feasible. By using the feedback temperature control system, magnetic nanoparticles can be heated up to the specific constant temperatures, 37, 40, 42, 45, 46 and 47degC, respectively, with a variation less than 0.2degC. With this approach, the in-vitro survival rate of tumour cells at different temperatures can be systematically explored. It was experimentally found that the survival rate of cancer cells can be greatly reduced while CT-26 cancer cells were heated above 45degC. Besides, localised temperatures increase as high as 59.5degC can be successfully generated in rat livers by using the proposed method. Finally, complete regression of tumour was achieved. The developed method used injectable magnetic nanoparticles and may provide a promising approach for hyperthermia cancer therapy.     

Polysaccharide-based magnetically responsive polyelectrolyte hydrogels for tissue engineering applications

Polysaccharide-based bionanocomposite hydrogels with functional nanomaterials were used in biomedical applications.Self-organization of xanthan gum and chitosan in the presence of iron oxide magnetic nanoparticles(Fe_3O_4MNPs)allowed us to form magnetically responsive polyelectrolyte complex hydrogels(MPECHs)via insitu ionic complexation using D-(+)-glucuronic acid?-lactone as a green acidifying agent.Characterization confirmed the successful formation of(and structural interactions within)the MPECH and good porous structure.The rheological behavior and compressive properties of the PECH and MPECH were measured.The results indicated that the incorporation of Fe_3O_4MNPs into the PECH greatly improved mechanical properties and storage modulus(G’).In vitro cell culture of NIH3T3 fibroblasts on MPECHs showed improvements in cell proliferation and adhesion in an external magnetic field relative to the pristine PECH.The results showed that the newly developed MPECH could potentially be used as a magnetically stimulated system in tissue engineering applications.     

Synthesis and characterizations of manganese ferrites for hyperthermia applications

In the last few years, magnetic nanoparticles have turned out to offer great potential in biomedical applications. This study was focused on Mn_xFe_1−xFe₂O₄ ferrite particles series with x ranging between 0 and 1. Manganese ferrites nanoparticles were prepared by co-precipitation method that allows a good control of their shape and size. The X-ray analysis indicated a crystallite size of the particles in the nanometers domain increasing with the Mn cation substitution level. Average grain size of the nanoparticles calculated from transmission electron microscopy images of the samples was ranging between 10.5 and 19.0 nm suggesting that the majority of the nanoparticles are monodomain. The hydrodynamic diameter of the water dispersed nanoparticles measured by dynamic light scattering was ranging between 60 and 105 nm proving the tendency of agglomeration. Vibrating sample magnetometer measurement confirmed the superparamagnetic behavior of the powders. The magnetic properties were analyzed considering the proposed cation distribution and Yafet–Kittel angles, while the specific absorption rate (SAR) measurement at 1.95 MHz frequency confirmed the influence of substitution level on magnetic properties and thermal transfer rate. From our results the highest value for specific absorption rate was 148.4 W g⁻¹ for Mn₂Fe₂O₄ at an AC field of 4500 A m⁻¹.     

Ultrasonic phased arrays with variable geometric focusing for hyperthermia applications

An ultrasonic applicator, which utilizes both electronic and variable geometric focusing, for deep-localized hyperthermia is investigated. The applicator is based around a linear phased array that furnishes its electronic focusing capability. The output of the array radiates through a spherical liquid-lens that provides the applicator a variable geometric focusing capability as well. A lens of this type adds dynamic focusing to the elevation dimension of the linear phased array. By controlling the volume of liquid in the lens (and thus the radius of curvature of its membrane), dynamic control of the geometrical focus can be achieved. Comparisons of computer simulations and experimental measurements of the field intensity distribution of a small-scale prototype applicator are presented. Important design parameters, such as the choice of the liquid for the lens and the size and number of array elements, are examined.     

Olive oil based novel thermo-reversible emulsion hydrogels for controlled delivery applications

Gels have been considered as a popular mode of delivering medicament for the treatment of sexually transmitted diseases (STDs) (e.g. human immunodeficiency virus, bacterial vaginosis, epididymitis, human papillomavirus infection and condylomata acuminata etc.). The present study discusses the development of novel olive oil based emulsion hydrogels (EHs) using sorbitan monopalmitate as the structuring agent. The developed EHs may be tried as drug delivery vehicle for the treatment of STDs. The formation of EHs was confirmed by fluorescence and confocal microscopy. FTIR studies suggested intermolecular hydrogen bonding amongst the components of the EHs. X-ray diffraction study suggested the amorphous nature of the EHs. The developed EHs have shown non-Newtonian flow behavior. The EHs were found to be biocompatible. The formulations were able to effectively deliver two model antimicrobial drugs (e.g. ciprofloxacin and metronidazole), commonly used in the treatment of the STDs.     

Inverse problem in the hyperthermia therapy of cancer with laser heating and plasmonic nanoparticles

In this paper, laser-induced hyperthermia therapy of cancer is treated as a state estimation problem and solved with a particle filter method, namely the Auxiliary Sampling Importance Resampling algorithm. In state estimation problems, the available measured data are used together with prior knowledge about the physical phenomena, in order to sequentially produce estimates of the desired dynamic variables. Although the hyperthermia treatment of cancer has been addressed in the literature by different computational methods, these usually involved deterministic analyses. On the other hand, state space representation of the problem in a Bayesian framework allows for the analyses of uncertainties present in the mathematical formulation of the problem, as well as in the measured data of observable variables that might be eventually available. Two physical problems are considered in this paper, involving the irradiation with a laser in the near infrared range of a non-homogeneous cylindrical medium representing either a soft-tissue phantom or a skin model, both containing a tumour. The region representing the tumour is assumed to be loaded with nanoparticles in order to enhance the hyperthermia effects and to limit such effects to the tumour. The light propagation problem is coupled with the bioheat transfer equation in the present study. Simulated transient temperature measurements are used in the inverse analysis.     

Energy absorption of gold nanoshells in hyperthermia therapy

The unique optical characteristics of a gold nanoshell motivate the application of nanoshell-based hyperthermia in drug delivery and cancer treatment. However, most of our understanding on energy absorption and heat transfer is still focused on individual particles, which may not be accurate for nanoshell aggregates in a real application due to the strong optical interaction of nanoshells. This paper investigates the relationship between the optical interaction and the interparticle distance in the visible and near-infrared regions by means of a finite-difference time-domain (FDTD) method. The objective is to explore the energy transportation mechanism, which is critical for hyperthermia therapy. From the numerical simulation results of different forms of nanoshell aggregates, including individual nanoshells, 1-D chains, 2-D arrays, and 3-D clusters, it was found that the interparticle distance plays a crucial role from the maximal absorption point of view. The interparticle distance affects both field enhancement and surface plasmon resonance position. The accurate prediction of energy absorption also helps the way nanoshells are populated in the tumor cell so as to prevent heat damage to healthy tissues in clinic applications. In the case of 3-D clusters, the laser energy decays exponentially along the wave propagation, and the penetration depth greatly depends on the interparticle distance. The closer the nanoshells are placed, the shorter the penetration depth is. The maximal total length for the laser penetration through the shell of gold nanoparticles is about a few hundred to several nanometers. The actual penetration depth primarily depends not only on the interparticle distance, but also on the size of the nanoshells as well as other factors. Since the absorption energy is concentrated on the surface clusters of nanoparticles, heat transfer mechanisms in metal-nanoparticles-based hyperthermia will differ from that in other hyperthermia. The information obtained from this paper will serve as a basis for further study of heat transfer in metal-nanoparticles-based hyperthermia.     

Poly(HEMA) hydrogels with controlled pore architecture for tissue regeneration applications

The technique for fabrication of soft porous hydrogels, in which both the size and the orientation of inner pores can be controlled, was developed. Three-dimensional hydrophilic gels based on poly[2-hydroxyethyl methacrylate] are designed as scaffolds for regeneration of soft tissues, e.g., nerve tissue. Anisotropic macropores of the size ranging from 10 to 50 μm were formed (1) by using a porogen-leaching method with a solid organic porogen, (2) by phase-separation during gelation in solvent-nonsolvent mixture, or (3) by combination of solid porogen elimination and phase-separation. As a porogen, poly(l-lactide) fibers were applied and consequently washed away under mild conditions to obtain desired spatial orientation of pores. Highly water-swollen polymer gels were characterized with high pressure (low vacuum) scanning electron microscopy (AquaSEM). The morphology of voids remaining after removing the solid PLLA porogen (the macropores) was clearly shown.     

Magnetic sensors and their applications

Magnetic sensors can be classified according to whether they measure the total magnetic field or the vector components of the magnetic field. The techniques used to produce both types of magnetic sensors encompass many aspects of physics and electronics. Here, we describe and compare most of the common technologies used for magnetic field sensing. These include search coil, fluxgate, optically pumped, nuclear precession, SQUID, Hall-effect, anisotropic magnetoresistance, giant magnetoresistance, magnetic tunnel junctions, giant magnetoimpedance, magnetostrictive/piezoelectric composites, magnetodiode, magnetotransistor, fiber optic, magnetooptic, and microelectromechanical systems-based magnetic sensors. The usage of these sensors in relation to working with or around Earth's magnetic field is also presented.     

Magnetic properties of cobalt-rare earth magnets for microwave applications

A family of sintered Co-rare earth alloys utilizing Sm, Pr, La, or Ce mischmetal has been developed. Each alloy is designed to optimize one of the following characteristics: 1) Magnets which exhibit magnetic energy products in excess of 20 MG . Oe; 2) Magnets which exhibit reversible demagnetization behavior in adverse fields up to 14 000 Oe; 3) Magnets using inexpensive rare earth metals to maximize the magnetic energy per unit cost. These alloys should extend the range of use of Co-rare earth magnets for microwave devices.     

Magnetic tunnel junctions for magnetic random access memory applications

Magnetic Tunnel Junctions (MTJ) are in the center of a large number of studies in spin polarized transport, because of their potential use in Magnetic Random Access Memory (MRAM) applications. The most commonly used tunnel junction is composed of an aluminium-oxide as a tunnel barrier and presents very interesting tunnel magnetoresistance (TMR) of about 40%. Nevertheless, this barrier needs an oxidation step and has a large resistance, which is not suitable for electronic devices. Thus a MTJ with an alternative ZnS barrier grown by sputtering on Si(111) substrate at room temperature is presented here with the following structure: Fe_{6 nm}Cu_{30 nm}(CoFe)_{1.8 nm}Ru_{0.8 nm}(CoFe)_{3 nm}ZnS_x(CoFe)_{1 nm}Fe_{4 nm}Cu_{10 nm}Ru_{3 nm}. The hard magnetic bottom electrode consists of the artificial antiferromagnetic structure in which the rigidity is ensured by the antiferromagnetic exchange coupling between two FeCo layers through a Ru spacer layer. This alternative barrier is most suitable for electronic devices and we will discuss its possible application in MRAM.     

New hydrogels based on maleilated collagen with potential applications in tissue engineering

New hydrogels based on maleic anhydride (MA) modified collagen were prepared with the aim of overcoming the high degradation rate displayed by collagen that is not otherwise chemically crosslinked. Semi-interpenetrated matrices were obtained by free radical polymerization of maleilated collagen (CM) and 2-hydroxyethyl methacrylate (HEMA) in the presence of ammonium persulfate (APS) and N,N,N′,N′-tetramethylethylenediamine (TEMED) as initiating system. The resulting matrices (CMH) had a sharp decrease in degradation, when compared to pure collagen. FTIR and H¹ NMR spectroscopies were used to confirm the incorporation of MA on the collagen peptide chains. The final composition of CMH was found to be strongly dependent by the concentration of maleilated collagen. The morphology of the hydrogels was studied by Scanning electron microscopy (SEM) and the macro-gel structure was confirmed. Water uptake of the synthetised hydrogels is influenced by both composition and the porosity of the matrices.     

Experimental methods of actuation, characterization and prototyping of hydrogels for bioMEMS/NEMS applications

As a member of the smart polymer material group, stimuli responsive hydrogels have achieved a wide range of applications in microfluidic devices, micro/nano bio and environmental sensors, biomechanics and drug delivery systems. To optimize the utilization of a hydrogel in various micro and nano applications it is essential to have a better understanding of its mechanical and electrical properties. This paper presents a review of the different techniques used to determine a hydrogel's mechanical properties, including tensile strength, compressive strength and shear modulus and the electrical properties including electrical conductivity and dielectric permittivity. Also explored the effect of various prototyping factors and the mechanisms by which these factors are used to alter the mechanical and electrical properties of a hydrogel. Finally, this review discusses a wide range of hydrogel fabrication techniques and methods used, to date, to actuate this family of smart polymer material.     

Magnetite nanoparticles with high heating efficiencies for application in the hyperthermia of cancer

Magnetic hyperthermia is a safe method for cancer therapy. A gap-type alternating current magnetic field (100 kHz, 100–300 Oe) is expected to be clinically applicable for magnetic hyperthermia. In this study, magnetite nanoparticles (MNPs) varying in size from 8 to 413 nm were synthesized using a chemical coprecipitation and an oxidation precipitation method to find the optimum particle size that shows a high heating efficiency in an applied magnetic field. The particles' in vitro heating efficiency in an agar phantom at an MNP concentration of 58 mg Fe/ml was measured in an applied magnetic field. In a magnetic field of 120 Oe, the temperature increase (ΔT) of the agar phantom within 30 s was 9.3 °C for MNPs with a size of 8 nm, but was less for the other samples, while in a magnetic field of 300 Oe, ΔT = 55 °C for MNPs with a size of 24 nm, and ΔT = 25 °C for MNPs with a size of 8 nm. The excellent heating efficiency of MNPs with a size of 24 nm in a magnetic field of 300 Oe may be due to a combination of the effects of both relaxation and hysteresis losses of the magnetic particles. It is believed that MNPs with a size of 8–24 nm will be useful for the in situ hyperthermia treatment of cancer.     

Formulation of chitosan-TPP-pDNA nanocapsules for gene therapy applications

The encapsulation of DNA inside nanoparticles meant for gene delivery applications is a challenging process where several parameters need to be modulated in order to design nanocapsules with specific tailored characteristics. The purpose of this study was to investigate and improve the formulation parameters of plasmid DNA (pDNA) loaded in chitosan nanocapsules using tripolyphosphate (TPP) as polyanionic crosslinker. Nanocapsule morphology and encapsulation efficiency were analyzed as a function of chitosan degree of deacetylation and chitosan-TPP ratio. The manipulation of these parameters influenced not only the particle size but also the encapsulation and release of pDNA. Consequently the transfection efficiency of the nanoparticulated systems was also enhanced with the optimization of the particle characteristics. Overall, the differently formulated nanoparticulated systems possess singular properties that can be employed according to the desired gene delivery application.     

"Nanohybrids" based on pH-responsive hydrogels and inorganic nanoparticles for drug delivery and sensor applications

Allyl-PEG capped inorganic NPs, including magnetic iron oxide (IONPs), fluorescent CdSe/ZnS quantum dots (QDs), and metallic gold (AuNPs of 5 and 10 nm) both individually and in combination, were covalently attached to pH-responsive poly(2-vinylpyridine-co-divinylbenzene) nanogels via a facile and robust one-step surfactant-free emulsion polymerization procedure. Control of the NPs associated to the nanogels was achieved by the late injection of the NPs to the polymerization solution at a stage when just polymeric radicals were present. Remarkably, by varying the total amount of NPs injected, the swelling behavior could be affected. Furthermore, the magnetic response as well as the optical features of the nanogels containing either IONPs or QDs could be modified. In addition, a radical quenching in case of gold nanoparticles was observed, thus affecting the final nanogel geometry.