Mechanical and Echogenic Properties of Spherical Ferrogels Based on Alginate and Magnetic Nanoparticles: Focus on Biomedical Applications

Nanotechnology offers tremendous potential for use in biomedical applications, including imaging, disease diagnosis, and drug delivery. The development of nanosystems has improved the molecular understanding of many diseases and permitted the controlled nanoscale manipulation of materials (Couvreur & Vauthier, 2006). Nanomedical platforms offer many advantages as delivery, sensing, and image-enhancing agents. In recent years, many studies have focused on multifunctional nanomedical platforms that incorporate therapeutic and diagnostic agents with molecular targeting capabilities. Gregoriadis et al. first proposed liposomes as drug carriers in cancer chemotherapy in 1974 (Gregoria et al., 1974). Today, drug delivery systems made of lipids or polymers frequently are exploited for the controlled delivery of therapeutic drugs in the body (Jain, 2005; Vasir et al., 2005). Nanosized particles for biomedical platforms can be made from a variety of materials, including lipids (liposomes, nanoemulsions, and solid-lipid nanoparticles), self-assembling amphiphilic molecules, nondegradable and degradable polymers, dendrimers, metals, and inorganic semiconductor nanocrystals. The selection of the platform material is determined by the desired diagnostic or therapeutic goal, payload type, material safety profile, and administration route. Among the various types of functional nanostructures, nanomedical platforms based on magnetic nanoparticles (MNPs) are of particular interest in biomedical applications. Most frequently, MNPs are constructed of superparamagnetic iron oxides (SPIOs) (e.g., Fe3O4 or γ-Fe2O3), although metals such as cobalt and nickel are also employed. The characteristics of MNPs, including their composition, size, morphology, and surface chemistry, are tailored by various processes for their wide application in the detection, diagnosis, and treatment of illnesses. The most popular MNPs for biomedical applications are comprised of a magnetic inorganic nanoparticle core and a biocompatible surface coating that provides stabilization under physiological conditions. The additional application of a suitable surface chemistry allows the integration of functional ligands, such that MNPs can perform multiple functions. The modification and functionalization of MNPs improve their magnetic properties and affect their behavior in vivo (Tartaj et al., 2003; A.K. Gupta & M. Gupta, 2005).

Through previous research, the excellent biocompatibility and bioactivity of calcium silicate were proven with the wide use in biomedical application. In this work, calcium silicate was synthesized from tetraethylorthosilicate (TEOS) and calcium nitrate tetrahydrate with calcium oxide: silicon dioxide (CaO: SiO2) ratio of 30:70 using sol-gel method. Chemical composition of CaO and SiO2 were analyzed using X-ray diffraction (XRD) and X-ray fluorescent (XRF). Magnetic Nanoparticles (MNPs) are gaining interest in all biomedical related application. However the usage of MNPs can’t be used directly and needed coating layer to improve the dispersion stability, biocompatibility and provide functionality. MNPs materials used in this research are maghemite (γ-Fe2O3). Maghemite was synthesized from ferrous chloride (FeCl3) and ferric chloride (FeCl2) with ratio FeCl3 to FeCl2 2:1 using sol gel method. Through this research, the potential of new coating materials which is calcium silicate to coat on maghemite while maintained the magnetic properties were studied and analyzed using VSM, XRD and XRF.Through previous research, the excellent biocompatibility and bioactivity of calcium silicate were proven with the wide use in biomedical application. In this work, calcium silicate was synthesized from tetraethylorthosilicate (TEOS) and calcium nitrate tetrahydrate with calcium oxide: silicon dioxide (CaO: SiO2) ratio of 30:70 using sol-gel method. Chemical composition of CaO and SiO2 were analyzed using X-ray diffraction (XRD) and X-ray fluorescent (XRF). Magnetic Nanoparticles (MNPs) are gaining interest in all biomedical related application. However the usage of MNPs can’t be used directly and needed coating layer to improve the dispersion stability, biocompatibility and provide functionality. MNPs materials used in this research are maghemite (γ-Fe2O3). Maghemite was synthesized from ferrous chloride (FeCl3) and ferric chloride (FeCl2) with ratio FeCl3 to FeCl2 2:1 using sol gel method. Through this research, the potential of new coating materials which is calcium silicate to coat on maghemite while ...

Magnetic engineering nanoparticles: Versatile tools revolutionizing biomedical applications

Magnetic nanoparticles with appropriate surface coatings are increasingly being used clinically for various biomedical applications, such as magnetic resonance imaging, hyperthermia, drug delivery, tissue repair, cell and tissue targeting and transfection. This is because of the nontoxicity and biocompatibility demand that mainly iron oxide-based materials are predominantly used, despite some attempts to develop 'more magnetic nanomaterials' based on cobalt, nickel, gadolinium and other compounds. For all these applications, the material used for surface coating of the magnetic particles must not only be nontoxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. Magnetic nanoparticles can bind to drugs and an external magnetic field can be applied to trap them in the target site. By attaching the targeting molecules, such as proteins or antibodies, at particles surfaces, the latter may be directed to any cell, tissue or tumor in the body. In this review, different polymers/molecules that can be used for nanoparticle coating to stabilize the suspensions of magnetic nanoparticles under in vitro and in vivo situations are discussed. Some selected proteins/targeting ligands that could be used for derivatizing magnetic nanoparticles are also explored. We have reviewed the various biomedical applications with some of the most recent uses of magnetic nanoparticles for early detection of cancer, diabetes and atherosclerosis.

This work reports the synthesis and toxicological evaluation of surface modified magnetic iron oxide nanoparticles as vehicles to carry and deliver nitric oxide (NO). The surface of the magnetic nanoparticles (MNPs) was coated with two thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) or dimercaptosuccinic acid (DMSA), leading to thiolated MNPs. Free thiols groups on the surface of MSA- or DMSA-MNPs were nitrosated leading to NO-releasing MNPs. The genotoxicity of thiolated-coated MNPs was evaluated towards human lymphocyte cells by the comet assay. No genotoxicity was observed due to exposure of human lymphocytes to MSA- or DMSA-MNPs, indicating that these nanovectors can be used as inert vehicles in drug delivery, in biomedical applications. On the other hand, NO-releasing MPNs showed genotoxicity and apoptotic activities towards human lymphocyte cell cultures. These results indicate that NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors, in which MNPs can be guided to the target site through the application of an external magnetic field, and release NO directly to the desired site of action.

Applications of magnetic targeting in diagnosis and therapy--possibilities and limitations: a mini-review.

Iron oxide based magnetic nanoparticles (MNPs) as typical theranostic nanoagents have been popularly used in various biomedical applications. Conventional core–shell MNPs are usually synthesized from inside to outside. This method has strict requirements on the interface properties of magnetic cores and the precursors of the coating shell. The shape and size of MNPs are significantly influenced by that of the pre-synthesized magnetic cores. Most core–shell MNPs have only single T2W MRI imaging ability. Herein, we propose a new synthetic strategy for core-mesoporous shell structural MNPs, where hollow mesoporous nanospheres which exhibit an intrinsic property for both CT imaging and drug loading were used as the shell and the magnetic cores were produced in the cavity of the shell. A new type of MNPs, Fe3O4@ZrO2 nanoparticles (M-MZNs), were developed using this facile outside-to-inside way, where multiple Fe3O4 nanoparticles grew inside the cavity of the mesoporous hollow ZrO2 nanospheres through chemical coprecipitation. The obtained MNPs not only exhibited superior magnetic properties and CT/MR imaging ability but also high drug loading capacity. In vitro experiment results revealed that M-MZNs-PEG loaded with doxorubicin (DOX) presented selective growth inhibition against cancer cells due to pH-sensitive DOX release and enhanced endocytosis by cancer cells under a magnetic field. Furthermore, the proposed MNPs exhibited CT/MRI dual modal imaging ability and effective physical targeting to tumor sites in vivo. More importantly, experiments of magnetic targeting chemotherapy on tumor bearing mice demonstrated that the nanocomposites significantly suppressed tumor growth without obvious pathological damage to major organs. Henceforth, this study provides a new strategy for CT/MRI dual-modal imaging guided and magnetic targeting cancer therapy.

In recent years, more and more attention has been paid to the development of various synthesis methods for magnetic nanoparticles and the study of their biomedical properties. The use of magnetic nanomaterials in medicine and pharmacology is a priority area of research, which allows to solve current problems related to the diagnosis and treatment of various diseases, including cancer. The use of magnetic nanoparticles simplifies the detection of affected areas of tissue at an early stage, targeted drug delivery, as well as therapy of pathological areas with the latest promising techniques. To date, oxide magnetic nanoparticles are of particular interest to medicine. They exhibit stable magnetic properties, are more resistant to oxidation than metal nanoparticles, and have low toxicity. Magnetic oxide nanoparticles, modified by different functional groups, are used in medicine as carriers of biologically active substances, as contrast materials for magnetic resonance imaging, as biosensors, as media for targeted delivery. In addition, magnetic nanoparticles have been used in thermal therapy (magnetic hyperthermia), which involves heating with ultrahigh-frequency radiation of cancer-affected tissue in combination with a magnetic field, which provides targeted delivery of nanoparticles to the cancer cells. The review summarizes the use of magnetic nanoparticles in biomedical applications. It describes the synthesis methods that will produce the nanoparticles with a narrow size distribution, high magnetic characteristics, stable composition and physical parameters. Due to low toxicity, iron oxides have recently been actively studied, especially their antibacterial properties. Various synthesis methods of oxide nanoparticles and their effect on biocidal properties have been presented. The main probable mechanisms of bacterial inactivation, particularly ROS generation, as well as membrane, DNA, protein and lipid damaging were considered. Fe oxides are potential nanomaterials for biomedical and industrial applications.KeywordsIron oxideAntibacterial propertiesBacterial inactivationDrug delivery

Since Democritus first proposed the hypothesis that matter was comprised of indivisible 'atoms', the concept of the atom has been constantly re-invented. In the early twentieth century the 'plum pudding' description of atomic structure as a sphere packed with 'currants' of positive and negative charge was replaced by a structure largely comprised of empty space with orbitals of electrons surrounding a nucleus of positive and neutral particles. In 1937 a group of investigators at Columbia University demonstrated that not only electrons but even neutrons possess an intrinsic magnetic moment [1]. Introducing a magnetic field on a liquid sample such as water, in which the nuclear magnetic moments of the protons are randomly oriented, causes a tiny surplus of the moments to become aligned parallel with the applied field. When this field is removed the sample releases a detectable signal. Nowadays such magnetic resonance effects are routinely used in medical imaging and diagnostics, and constitute a field of fruitful activity in nanotechnology research.As with most physical concepts, magnetic properties of materials reveal various subtle intricacies as the dimensions are scaled down to nanometer sizes. In very small magnetic materials less than 50 nm in size the magnetic moment can reorient spontaneously, an effect referred to as superparamagnetism, first demonstrated by Elmore at Massachusetts Institute of Technology [2]. Advances in nanoparticle synthesis procedures have allowed greater control in the distribution of physical parameters, such as size, shape, crystallinity and coating, making it possible to study the effect that varying these parameters has on the magnetic properties, such as the saturation magnetization and susceptibility [3].There has also been progress in developing techniques to prepare magnetic nanoparticles in different forms, such as stably dispersed in an aqueous solution [4]. The ability to form a stable aqueous dispersion of magnetic nanomaterials is essential for a wide range of environmental and biomedical applications, including magnetic resonance imaging. The magnetic nanoparticles used in magnetic resonance imaging have themselves become increasingly sophisticated. Size effects can be exploited, and dextran coatings have been used to allow the particles to be conjugated with a variety of antibodies, peptides and proteins for targeting specific tissues [5]. However the dextran coating contributes significantly to the particle's size, which may limit tissue distribution and metabolic clearance. An alternative is to coat magnetic iron nanoparticles with gold. The gold can be conjugated with biomolecules and provides a potential platform for optical absorption and emission caused by the collective electronic response of the metal to light [6].The optical contrast potential of gold-coated nanoparticles has now been demonstrated by researchers in Texas [7]. The plasmonic gold layer presents opportunities for use in photothermal therapy applications. The thermoresponse of magnetic nanoparticles has been the subject of much promising research activity and hyperthermia cancer treatment has been demonstrated using multimodal magnetic nanoparticles [8,9]. In the US, a collaboration of researchers has developed a new multimodal technique that uses ultrasound imaging of magneto-motive excitation to identify tissue-based macrophages containing iron oxide nanoparticles [10].The potential of magnetic nanoparticles has beguiled many scientists into highly rewarding avenues of research over recent years. In this issue researchers at the Tokyo Institute of Technology and Toyohashi University of Technology provide an overview of the role of functionalized magnetic nanoparticles in biorecognition and medical diagnostics [11]. The review covers topics from synthesis and functionalization procedures to Hall biosensors and a label-less homogenous procedure referred to as 'magneto-optical transmission sensing', where the optical transmission of a solution containing rotating linear chains of magnetic nanobeads is used to detect biomolecules with picomolar sensitivity and a dynamic range of more than four orders of magnitude.In 1944 Isidor Isaac Rabi won the Nobel Prize for physics in recognition of his work in developing a resonance method for recording the magnetic properties of atomic nuclei. He recognized the possible application of his work in time keeping but it was not until the work of later researchers that the potential in medical imaging became apparent. Decades later, in 1988 Rabi was reported to have said: 'It was eerie. I saw myself in that machine. I never thought my work would come to this' [12]. The comment was provoked by the sight of a distorted image of his face, reflected on the inside cylindrical surface of a magnetic resonance imaging machine. Rabi died a few weeks later, but his work and that of fellow scientists have brought advances in medical imaging that have enabled the detection of malignant disease at early treatable stages. That his contribution has allowed timely diagnosis and treatments that have saved countless lives brings an added poignancy to his words. And there are, no doubt, many more breakthroughs in medicine and technology to come.

To modulate the properties of degradable implants from outside of the human body represents a major challenge in the field of biomaterials. Polylactic acid is one of the most used polymers in biomedical applications, but it tends to lose its mechanical properties too quickly during degradation. In the present study, a way to reinforce poly-L lactic acid (PLLA) with magnetic nanoparticles (MNPs) that have the capacity to heat under radiofrequency electromagnetic fields (EMF) is proposed. As mechanical and degradation properties are related to the crystallinity of PLLA, the aim of the work was to explore the possibility of modifying the structure of the polymer through the heating of the reinforcing MNPs by EMF within the biological limit range f·H < 5·× 109 Am−1·s−1. Composites were prepared by dispersing MNPs under sonication in a solution of PLLA. The heat released by the MNPs was monitored by an infrared camera and changes in the polymer were analyzed with differential scanning calorimetry and nanoindentation techniques. The crystallinity, hardness, and elastic modulus of nanocomposites increase with EMF treatment.

Magnetic nanoparticles (NPs) are increasingly important in many biomedical applications, such as drug delivery, hyperthermia, and magnetic resonance imaging (MRI) contrast enhancement. To build the most effective magnetic nanoparticle systems for various biomedical applications, characteristics of particle, including size, surface chemistry, magnetic properties, and toxicity have to be fully investigated. In this work, comparison of some magnetic multicomponent nanoparticles for bio-medical applications is discussed. In this investigation, multi-component ferrite nanoparticles were prepared by the hydrothermal synthesis, sol-gel, and solid state methods. In addition, x-ray powder diffractometry (XRD), scanning electron microscopy (SEM), and Quantum Design Physical Properties System (PPMS) were used to characterize the structural, morphological and magnetic properties of the nanoparticles. The size and crystal structure of the nanoparticles were characterized by using XRD results. The magnetic properties of the samples were performed for each sample at ± 1.5 T by PPMS.

Chapter 16 - Biomedical applications of magnetic nanoparticles

Nitric oxide (NO) is involved in several physiological and pathophysiological processes, such as control of vascular tone and immune responses against microbes. Thus, there is great interest in the development of NO-releasing materials to carry and deliver NO for biomedical applications. Magnetic iron oxide nanoparticles have been used in important pharmacological applications, including drug-delivery. In this work, magnetic iron oxide nanoparticles were coated with thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) and dimercaptosuccinic acid (DMSA). Free thiol groups on the surface of MSA- or DMSA- coated nanoparticles were nitrosated, leading to the formation of NO-releasing iron oxide nanoparticles. The cytotoxicity of MSA- or DMSA-coated magnetic nanoparticles (MNP) (thiolated nanoparticles) and nitrosated MSA- or nitrosated DMSA- coated MNPs (NO-releasing nanoparticles) were evaluated towards human lymphocytes. The results showed that MNP-MSA and MNP-DMSA have low cytotoxicity effects. On the other hand, NO-releasing MNPs were found to increase apoptosis and cell death compared to free NO-nanoparticles. Therefore, the cytotoxicity effects observed for NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors cells.

Biomedical applications of biodegradable polycaprolactone-functionalized magnetic iron oxides nanoparticles and their polymer nanocomposites

Fe3O4 and Fe3O4@SiO2 magnetic nanoparticles (MNPs) have recently become important in biomedical applications; however, influences of these MNPs to cells are still not very clear. Bare Fe3O4 and Fe3O4@SiO2 MNPs should be noticed because any surface modification may be removed from them when they enter into cells or in cells. In this work, in order to avoid too much surface residues from the precursors, coprecipitation method is adopted to synthesize bare Fe3O4 MNPs, while Stober process is performed to synthesize bare Fe3O4@SiO2 MNPs. The characterization of MNPs is indentified by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), X-ray Absorption Spectroscopy (XAS) and Superconducting Quantum Interference Device Magnetometer (SQUID). These results show that as-prepared Fe3O4 MNPs primarily contains crystalline Fe3O4 phase, while the deposited SiO2 on Fe3O4 MNPs is amorphous. A549 lung cancer cells are used as model cells for MNPs treatment, and the cell viability is measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results show that mitochondrial reductase activity in cells is reduced by treating Fe3O4 MNPs and Fe3O4@SiO2 MNPs to A549 cells for 36 hr. Instead of traditional biochemical methods, synchrotron radiation infrared-ray (SRIR) spectra and synchrotron radiation infrared-ray microscopy (SRIRM) with high spatial resolution 10μm are carried out to measure the change of chemical components and chemical composition distribution in cells. These results exhibit that DNA structures in cells are indirectly affected by Fe3O4 MNPs and Fe3O4@SiO2 MNPs, and the concentration of DNA becomes less with MNPs concentration and treatment time while no protein and lipid changes are observed, but the lipid/protein ratio is MNPs-concentration-dependent and treatment-time-dependent and it is observed that the amount of lipids is relatively larger at far-nucleus regions while that of proteins is relative larger at and around the nucleus region.