Encyclopedia
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects:
Biochemical Research Methods
Iron oxide nanoparticles (IONPs) and superparamagnetic iron oxide nanoparticles (SPIONs) are magnetics nanoparticles (MNPs) that have received extensive attention because of their physicochemical and magnetic properties and their ease of combination with organic or inorganic compounds. Commonly, MNPs act as a reinforcing material for the polymer matrix.
- iron oxide nanoparticles
- superparamagnetic iron oxide nanoparticles
- hydrogels
- magnetic nanoparticles
- nanocomposites
- synthesis
- characterization
1. Introduction
For a few decades, growing chemical synthesis of nanomaterials and material surface modification have been observed and performed in numerous applications, including biomedicine, biotechnology, catalysis, magnetic chemistry thermoelectric materials, etc. [1]. Nanoparticles (NPs) are a kind of nanomaterial that have attracted the interest of scientists. According to the synthesis method, NPs with different compositions, shapes, sizes, size distributions, and properties can be obtained. One of the most important and studied NPs is the magnetics nanoparticle (MNP). The unique physicochemical properties of MNPs, especially their large surface areas, ease of synthesis and modification, and inherent superparamagnetic properties, could lead to improved technologies [2]. Moreover, these MNPs present an excellent capability to achieve a synergic union with other compounds, such as polymers [3].
Polymers can adopt a cross-linked matrix known as a hydrogel depending on the polymerization method. Hydrogels have widespread use in tissue engineering and functional devices because of their biomimetic properties and multi functionalities [4]. A hydrogel can be defined as a three-dimensional cross-linked polymer network that can absorb and retain a large amount of water [5] and active components [6], such as NPs.
Magnetic materials have been studied in recent years for their potent versatility. IONPs emerged as a promising material due to their magnetic properties, the superparamagnetism that leads to very high relativity, high biocompatibility, and easy functionalization of their surfaces with target molecules [7]. Several methods have been considered for synthetizing IONPs [8] by obtaining MNPs of different shapes and sizes. Moreover, based on their size, IONPs can be classified into three categories: micrometer-sized (300–3.5 µm), standard-sized (10–150 nm), and ultra-small (<10 nm) iron oxide crystals. Moreover, MNPs can be classified according to their magnetic properties as IONPs and SPIONs. Moreover, SPIONs are a kind of IONPs with remarkable magnetic properties. The great advantage of SPIONs is their magnetic properties that allow direct delivery of matter into the pathogen zone without influencing the whole organism [9].
The functionalization of the MNPs with organic and inorganic materials is indispensable for its applications. IONPs and SPIONs have an iron oxide core coated by an organic or inorganic layer [10] or encapsulated in a polymeric matrix. MNPs are usually functionalized with proteins (amino group), silica, polymer, surfactants, and organic materials to reduce toxicity and optimally fulfill their biomedical functions in drug delivery applications [11]. IONPs have been used to tailor the properties of polymeric hydrogels [12]; meanwhile, the hydrogels acquire a magnetic response. These hydrogels are subjected to reversible changes in their microstructure, as they can go from a compressed state to a swollen state by responding to an external magnetic field [13].
2. Iron Oxide Nanoparticles (IONPs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs)
IONPs and SPIONs are attractive materials with excellent properties and magnetic tenability, making them suitable for biomedical approaches [18]. IONPs have attracted widespread attention due to their biocompatibility, low cost, chemically stable, and unique magnetic features. Meanwhile, SPIONs are IONPs with enhanced magnetic properties. In addition, SPIONs are nanomaterials characterized as chemically inert materials which decrease toxicity. They are characterized by a superparamagnetic character and immune induction capacity, making them a potential charger for antigen delivery [19].
These magnetic materials present unique intrinsic magnetic properties known as superparamagnetism and high colloidal stability, making them very attractive in a wide range of uses [20], with an approach to magnetic resonance imaging. Moreover, they can be obtained by employing different chemical methods, where IONPs without any surface coating (un-functionalized) are not stable in aqueous media, resulting in a readily aggregate and precipitate [21]. The colloidal suspension of iron oxides (un-functionalized), particularly magnetite, is easily oxidized in air and susceptible to loss of magnetism [11]. Similarly, bare SPIONs may be toxic because they are chemically reactive, so the coating layer prevents aggregation and agglomeration of the NPs and reduces iron oxide oxidation [10]. To overcome this issue, surface modification and a combination of other materials to develop new nanocomplexes through a highly engineered process can combat the physiological barrier [18]. For example, Figure 1 illustrates a general representation of MNPs combined with other materials.
Figure 1. Schematic representation of magnetic nanoparticle.
2.1. Funcionalization
One of the most critical topics in designing MNPs for in vivo applications is functionalization, which provides NPs with high stability in physiological media, stealth, and vector targeting properties [26], because IONPs and SPIONs are highly reactive species with oxidizing agents such as air. Moreover, bare iron oxide has a significant toxicity effect [12], and the SPIONs have an efficiency limited by the tendency to be agglomerated. Therefore, the addition of surfactants and protective agents can serve as an appropriate surface coating to control IONPs and SPIONs stability, biocompatibility and achieve an appropriate functionalization [27,28]. In general, there are two types of structural configurations; one is magnetic core with a biocompatible polymer as coating, and the other is porous biocompatible polymer, in which the MNPs can diffuse through the pores [29].
2.2. Properties
Among the magnetic IONPs family, the three most popular M-IONPs are magnetite (Fe3O4), maghemite (γ-Fe2O3), and hematite (α-Fe2O3) [40]. The main characteristic of these magnetic IONPs is their strong magnetism. This phenomenon corresponds to ferrimagnetism: the magnetic moments of the different iron cations in the system are strongly coupled by antiferromagnetic interactions, but in such a way that an uncompensated magnetic moment results in each unit cell [41]. In magnetite, the Fe ions exist in the valence state +2 and +3 in a ratio of 1:2. For each Fe2+ and Fe3+ ions, a magnetic moment corresponds to four and five Bohr magnetons, respectively, for both types of ions. In addition, O2− ions are magnetically neutral. The critical factor is the distribution of the spin moments of the Fe ions. The spin moments of all the Fe3+ ions at the octahedral positions are aligned parallel to each other [40]; however, they are directed opposite the Fe3+ ions of the tetrahedral positions, which are also aligned. This phenomenon occurs due to the antiparallel coupling of the magnetic moments of the adjacent Fe ions. Therefore, the spin magnetic moments of all Fe3+ ions cancel each other out and do not contribute to the magnetization of the solid [42].
2.3. Properties Associated with Polymers
The main issue of MNPs concerning their size scales is long-term inherent instability, which occurs in two main routes: (1) dispersibility loss, where bare MNPs tend to agglomerate due to Van der Waals forces, overcoming the high surface energy and the strong magnetic attraction between particles and (2) magnetism loss, where oxidation of MNPs occurs [40,51]. These issues can be solved by the MNPs’ functionalization or by encapsulating of these MNPs into a polymeric cross-linked structure (hydrogel) known as magnetic nanocomposites (MNCs), which can also be called magnetic gels, ferrogel, or magnetoelastic gels [52]. Combining the reinforcement material and the matrix supporting the reinforcement material in the composite material, results in a better performance [3], reduces cytotoxicity, increases either the cytocompatibility and bio-conjugation [40], and improves the mechanical properties of the polymeric matrix.
The hydrogel can be chemical (covalent bonds) or physically (Van der Walls interaction) synthesized [53], adopting a three-dimensional structure, which is cross-linking through their chains. However, higher concentrations of IONPs formed more cross-links between the NPs and polymer, leading to stiffer, tougher nanocomposite hydrogels and enhanced electrical conductivity than smaller concentrations of IONPs that displays a lower cross-linked density [13].
3. Methods of Preparation
3.1. Synthesis of Magnetite Iron Oxide Nanoparticles
IONPs can be synthesized easily using chemical approaches such as co-precipitation, thermal decomposition, sol-gel process [57], hydrothermal [58] and polyol methods, etc. These methods require the salts of Fe2+ or Fe3+ ions or organic iron precursors and stabilizing agents that control particle size and prevent agglomeration. Unfortunately, most IONP synthesis methods involve an organic medium, making its application difficult in biological systems, whose main component is water.
The physical and chemical properties of the NPs can be controlled according to the synthesis method used to obtain the desired NPs for the desired application. In this way, monodisperse IONPs with various morphologies, including nanospheres, plates, tetrahedrons, cubes, truncated octahedrons, octahedrons, concaves, and multi branches have been successfully fabricated under different synthesis protocols [7].
3.2. Fabrication of Hydrogel Magnetite Nanocomposite
The polymeric matrix known as hydrogel is prepared from the association of multiple monomer bonds to form long polymers chains that can uptake large amounts of water and other solvents [53]. Hydrophilic polymers might be considered to be those polymers that contain polar functional groups such as hydroxyl (–OH), carboxyl (–COOH), and amino (–NH2) groups that make them soluble or swelled by water [87]. Hydrogels are porous, soft, and biocompatible materials with a soft consistency similar to natural tissues. Despite their properties, low thermal stability, and poor mechanical strength constitute limitations of the hydrogel applications in biomedicine [90]
Hydrogel nanocomposites are composed of three-dimensional polymer networks, which show excellent performance due to incorporating inorganic NPs in the porous internal structure. Composite hydrogels have gained significant attention because of their enhanced intrinsic mechanical strength and bioactivity compared to pure hydrogels [91].
4. Characterization
Fundamental techniques employed to investigate the IONs immersed in hydrogels include X-ray Diffraction, Fourier Transform Infrared Spectroscopy, Transmission Electron Microscopy, Scanning Electron Microscopy, Atomic Force Microscopy, Vibrating Sample Magnetometer, and Thermogravimetric Analysis, among others.
4.1. Structural Analysis
4.1.1. Transmission Electron Microscopy (TEM)
Transmission electron microscopy involves diffraction, imaging, or spectroscopy performed with high-energy electrons in transmission geometry. It works by detecting transmitted electrons carriers of information about IONPs inner structure [30]. It is a technique employed to study NPs morphology (shape-size), dispersion, and quality [106].
4.1.2. Fourier Transform Infrared Spectroscopy (FTIR)
FTIR is a technique used to characterize certain chemical groups in the hydrogel networks. The spectrum obtained through this technique shows vibration bands correlated with bonds or functional groups that are useful to identify unknown compounds. For the characterization of polymeric composites with IONPs, FTIR allows identifying the composition and functional groups involved in the capping and stabilization of the MNPs [110].
4.1.3. Small Angle Neutron Scattering (SANS)
Small angle neutron scattering (SANS) is a valuable technique to study magnetic and internal structural properties in nanostructures ensembles. This technique is based on the direct interaction between neutrons and the atomic nuclei, which produce a scattering length associated with specific elements [115]. It is necessary to have adequate experimental conditions such as a sample with a solvent with scattering contrast variations, which allows identifying magnetic scattering or elemental composition of individual layers [116].
4.2. Magnetometric Methods
Magnetic Response Measurements
Materials generally show magnetism only in the presence of an applied field. However, certain materials exhibit ordered magnetic states in the absence of an applied field. Those materials that present magnetization without a magnetic field are ferro or ferrimagnets. Based on the magnetic susceptibility, there is a general classification: paramagnetic and diamagnetic.
The most common characterization techniques to measure magnetic parameters of IONPs are Vibrating Sample Magnetometer (VSM) and Superconducting Quantum Interference Device (SQUID). Saturation magnetization, remnant magnetization, and the coercive field are some magnetic parameters that can be deduced from hysteresis loops. Moreover, it helps identify the type of magnetism presented, such as diamagnetism, paramagnetism, ferromagnetism, antiferromagnetism, and ferrimagnetism [30]. MNPs are known for their superparamagnetic properties. When MNPs apply magnetic field, they show colloidal behavior but uniform dispersion when the applied field is retired [126].
4.3. Swelling Analysis
The swelling properties are used to define the characteristics of hydrogels. Some factors related are network density and polymer-solvent interaction parameters. Hydrogels are soft and wet polymeric materials, showing a finite swelling capacity. In the 1940s, the research of 1094 Nobel laureate Paul Flory led to a detailed, fundamental understanding of the hydrogels’ cross-linked structure, their swelling/syneresis characteristics, and the small and large deformation behavior in pure water and physiological fluids [127]. The ability of gels to retain fluids could be analyzed through swelling behavior characterization. The swelling capacity of hydrogels varies considerably depending on different factors.
4.4. Cytotoxicity Analysis
Many synthetic methods to produce the MNPs could produce cytotoxic effects caused by free-radical production and high iron dosage. Previous studies reported that a dose level of iron up to 100 µg/mL results in nontoxic effects in vivo and in vitro conditions. Biocompatible composites could be produced by ligand exchange or encapsulation methods, where water-dispersible IONPs are obtained [130]. Polymeric hydrogels have numerous potential applications, but they require a previous cytotoxic analysis. Their characterization can be carried out directly or indirectly. The direct form involves direct contact tests with the cells, such as human epithelial cells, and the indirect ones are carried out with the growth of cells in polystyrene plates [131].
5. Applications
There is an interest in IONPs with polymers obtained from natural sources due to their higher biocompatibility which implies the potential use on biomedicine. NPs are commonly used in different biomedical applications because of their anticancer, antimicrobial, antiviral, antiplasmodial properties. Moreover, magnetic iron oxide is already approved by the food and drug administration (FDA) for medical and food applications, making IONPs good candidates to study their biofilm inhibitory properties [132].
MNPs have been used in biomedicine since the 1990s. The fact that iron is easily metabolized within the body that the particles have sizes comparable to that of proteins, cells, viruses and DNA that the surface of these particles can be modified in order to bind molecules of biological interest that particles possess a high magnetic moment, as well as the fact that the field lines can cross the human body, means that the particles hold a promising future in the search for minimally invasive methodologies to assist in the diagnosis and treatment of diseases.
5.1. In Vivo Applications
MNPs must be compatible and easily biodegraded in the body for therapeutic applications. In IONPs, after being metabolized, iron ions are added from the body’s iron stores and are finally incorporated by erythrocytes as part of hemoglobin. Of these particles, hardly any harmful effects have been described. The cytotoxic effects observed due to the ingestion of this type of particles only occur at high concentrations (greater than 100 ug/mL) [135]. Two types of superparamagnetic IONPs are used: SPIONs and USPIONs (Ultra SuperParamagnetic IONPs), differences only in size (USPIONs, <50 nm; SPIONs, >50 nm).
Size plays a crucial role in biodistribution in vivo since the residence time in the organism depends on the size of the particle. According to the therapeutic purpose of the administration of the MNPs, a parameter to be taken into consideration for them to be of interest from the clinical point of view is that the circulation time in the blood after being injected into the body is long enough to that they can achieve their desired goals [136].
5.2. In Vitro Applications
Separation and Selection
Solid-phase extraction (SPE) is highly popular as an efficient system for isolating and pre-concentrating the desired components of an analytical sample, providing an excellent alternative to conventional concentration methods such as liquid-liquid extraction. For example, SPE is a routine extraction method for determining trace level contaminants in environmental samples. However, the separation and preconcentration of a substance present in large volumes of the solution are time-consuming when using a standard SPE column.
6. Conclusions
IONPs and SPIONs are MNPs with highly magnetic properties. These NPs can be obtained by co-precipitation, polyol, hydrothermal, microemulsion, and sol-gel methods, which require iron ions as precursors and stabilizing agents. These MNPs display different physicochemical properties, which can be controlled by adjusting the synthesis parameters such as temperature, molar ratio, precursors, reaction time, etc. The most conventional method to prepare MNPs is co-precipitation due to ease of manufacture and reproducibility. Despite their potential features, these MNPs present some disadvantages, such as toxicity not being stable in aqueous media, resulting in easy aggregation and precipitation. Therefore, to overcome this problem, MNPs must be coated or encapsulated with surfactants, protective agents, or cross-linking matrixes to improve their properties. A synergistic approach between MNPs and hydrogels would enhance the performance of both materials.
Hydrogels are known for their smart response when subjected to an external change. In this case, when hydrogels are combined with MNPs, they form a magnetic composite that adopts a magnetic behavior, showing a stimuli-response when subjected to a magnetic field. The synthesis of these composites is based mainly on blending, in situ precipitation, and grafting methods, where the blending method is the most common to produce magnetic hydrogels. Blending and in situ precipitation are low cost and straightforward methods for synthesizing magnetic composites. In contrast, the grafting-onto method requires an expensive and struggling manufacturing process. In addition, some characterization techniques are necessary to understand and study the functional groups’ surface morphology, chemical composition, and spatial distribution.
These MNPs are highly used in in vivo and in vitro applications in biomedicine. They show a better diagnosis performance, mainly as MIR, because MNPs are used as contrast agents. Moreover, they are highly used in drug delivery. When these NPs are functionalized with polymers, they can interact with bioactive molecules that recognize targets and act on specific sites.
This entry is adapted from the peer-reviewed paper 10.3390/polym14040752
This entry is offline, you can click here to edit this entry!
