Magnetic Nanoparticle-Mediated Heating for Biomedical Applications

Magnetic iron oxide nanoparticles have become the main candidates for biomedical and biological applications, and the application of small iron oxide nanoparticles in in vitro diagnostics has been practiced for about half a century. Magnetic nanoparticles (MNPs), in combination with an external magnetic field and/or magnetizable grafts, allow the delivery of particles to the chosen target area, fix them at the local site while the medication is released, and act locally. In this review, we focus mostly on the potential use of MNPs for biomedical and biotechnological applications, and the improvements made in using these nanoparticles (NPs) in biological applications.

Magnetic nanoparticles: In vivo cancer diagnosis and therapy

The synthesis of magnetic nanoparticles (MNPs) coated with hydrophilic poly-sodium-acrylate (PSA) ligands was studied to assess PSA-MNP complexes as draw solution (DS) solutes in forward osmosis (FO). For MNP-based DS, the surface modification and the size of the MNPs are two crucial factors to achieve a high osmolality. Superparamagnetic nanoparticles (NP) with functional groups attached may represent the ideal DS where chemical modifications of the NPs can be used in optimizing the DS osmolality and the magnetic properties allows for efficient recovery (DS re-concentration) using an external magnetic field. In this study MNPs with diameters of 4 nm have been prepared by controlled chemical co-precipitation of magnetite phase from aqueous solutions containing suitable salts of Fe2+ and Fe3+ under inert atmosphere and a pure magnetite phase could be verified by X-ray diffraction. Magnetic colloid suspensions containing PSA-coated MNPs with three different molar ratios of PSA:MNP = 1:1, 1:2 and 1:3 were prepared and assessed in terms of osmotic pressure, aggregation propensity and magnetization. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the presence of PSA on coated MNPs and pristine PSA-MNPs with a molar ratio PSA:MNP = 1:1 exhibited an osmotic pressure of 30 bar. Molar ratios of PSA:MNP = 1:2 and 1:3 lead to the formation of less stabile magnetic colloid solutions, which led to the formation of aggregates with larger average hydrodynamic sizes and modest osmotic pressures (5.5 bar and 0.2 bar, respectively). After purification with ultrafiltration, the 1:1 nanoparticles exhibited an osmotic pressure of 9 bar with no aggregation and a sufficient magnetization of 25 emu/g to allow for DS regeneration using an external magnetic field. However, it was observed that the amount of PSA molecules attached to the MNPs decreased during DS recycling steps, leaving only strong chelate-bonded core-shell PSA as coating on the MNPs. This demonstrates the crucial role of MNP coating robustness in designing an efficient MNP-based DS for FO.

Nowadays the use of magnetic nanoparticles (MNP) in medical applications has exceeded expectations. In molecular imaging, MNP based on iron oxide coated with appropriated materials have several applications in vitro and in vivo studies. For applications in nanobiotechnology these MNP must present some characteristics such as size smaller than 100 nanometers, high magnetization values, among others. Therefore the MNP have physical and chemical properties that are specific to certain studies which must be characterized for quality control of the nanostructured material. This study presents the synthesis and characterization of MNP of magnetite (Fe3O4) dispersible in water with perspectives in a wide range of biomedical applications. The characterization of the colloidal suspension based on MNP stated that the average diameter is (12.6±0.2) nm determined by Transmission Electron Microscopy where the MNP have the crystalline phase of magnetite (Fe3O4) that was identified by Diffraction X-ray and confirmed by Mossbauer Spectroscopy. The blocking temperature of (89±1) K, Fe3O4 MNP property, was determined from magnetic measurements based on the Zero Field Cooled and Field Cooled methods. The hysteresis loops were measured at different temperatures below and above blocking temperature. The magnetometry determined that the MNP showed superparamagnetic behavior confirmed by ferromagnetic resonance.

Biomedical Applications of Magnetic Nanoparticles

One of the major challenges in medicine is the rapid and accurate measurement of protein biomarkers, cells, and pathogens in biological samples. A number of new diagnostic platforms have recently been developed to measure biomolecules and cells with high sensitivity that could enable early disease detection or provide valuable insights into biology at the systems level. Most biological samples exhibit negligible magnetic susceptibility; therefore, magnetic nanoparticles have been used for diverse applications including biosensing, magnetic separation, and thermal ablation therapy. This review focuses on the use of magnetic nanoparticles for detection of biomolecules and cells based on magnetic resonance effects using a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells. The core principle behind DMR is the use of magnetic nanoparticles as proximity sensors that modulate the spin-spin relaxation time of neighboring water molecules, which can be quantified using clinical MRI scanners or benchtop nuclear magnetic resonance (NMR) relaxometers. Recently, the capabilities of DMR technology were advanced considerably with the development of miniaturized, chip-based NMR (microNMR) detector systems that are capable of performing highly sensitive measurements on microliter sample volumes and in multiplexed format. With these and future advances in mind, DMR biosensor technology holds considerable promise to provide a high-throughput, low-cost, and portable platform for large scale molecular and cellular screening in clinical and point-of-care settings.

Magnetic Nanoparticles (MNPs) have gained interest within the research community due to their therapeutic potential in a variety of medical applications. MNPs are generally composed of a metallic core stabilized by the addition of an outer shell that can be further functionalized through the absorbance or conjugation of various targeting ligands. The magnetic properties of these nanoparticles can be utilized for imaging, localized drug delivery, and enhanced diagnostic detection. This chapter highlights the applications of MNPs to enhance magnetic resonance imaging (MRI) capabilities and improve the delivery of therapeutic agents to difficult-to-reach areas in the body. In addition, recent advances in the use of MNPs in stem cell therapy for both the tracking and monitoring of stem cell distribution in the body and improving engraftment and differentiation in stem cell therapy are discussed. Finally, examples of the incorporation of MNPs in diagnostic assays to improve rapid and realtime detection capabilities of many diseases, including cancer, cardiovascular diseases, and pathogen infections, are provided.

Magnetic induction heating of superparamagnetic nanoparticles during rewarming augments the recovery of hUCM-MSCs cryopreserved by vitrification

20 - Environmental applications of magnetic nanoparticles

Polymer flooding is a proven technology to improve sweep efficiency, while being one of the most economical enhanced oil recovery (EOR) processes. Partially hydrolyzed polyacrylamide (HPAM) has been widely used for polymer flooding. As the HPAM usage for EOR increases, the challenge of produced water management is also raised because residual HPAM in produced water could increase total chemical oxygen demand and unwanted viscosity in discharging or re-injecting the water. As the environmental standards and regulations get more stringent, it is difficult for the conventional methods to meet the requirement for discharging. Use of magnetic nanoparticles (MNPs) to remove contaminants from produced water is a promising way to treat produced water in an environmentally green way with minimal use of chemicals. The main attraction for MNPs is their quick response to move in a desired direction with application of external magnetic field. Another attraction of MNPs is versatile and efficient surface modification through suitable polymer coating, depending on the characteristics of target contaminants. In this study, we investigate the feasibility of polymer removal using surface-modified MNPs and regeneration of spent MNPs for multiple re-use. MNPs, in-house synthesized with prescribed surface coating, were superparamagnetic with an average individual particle size of ~10 nm. The removal efficiency of HPAM from water using the MNPs depended on the type and concentration of brines, concentration of amine-functionalized MNPs, surface coating of MNPs, molecular weight of polymer, and how many times the MNPs are regenerated and re-used. Virtually 100% removal of HPAM from water was feasible, depending on the reaction conditions. The regeneration of spent MNPs, using pH adjustment to recover the reactive sites, maintained above 90% removal efficiency for three-time repeatitive usages. The electrostatic attraction between negatively charged HPAM polymer and positively charged MNPs controls the attachment of MNPs to HPAM molecular chain; and the subsequent aggregation of the now neutralized MNP-attached HPAM plays a critical role for accelerated and efficient magnetic separation.

Bromate, often detected in drinking water, is associated with a significant risk of cancer. Catalytic reduction has been recognized as an effective treatment technique to remove ions by reducing them over metal catalysts in the presence of a reducing agent, usually hydrogen. This work aims to synthesize metallic magnetic nanoparticles of iron oxide (FeO) and mixed iron oxides with manganese (MnFeO), cobalt (CoFeO), and copper (CuFeO) coated with carbon via chemical vapor deposition (C-MNP) to be applied as catalysts to the reduction of bromate in water. The use of magnetic nanoparticles coated with carbon enables catalyst recovery via magnetic separation and takes advantage of the catalytic properties of the carbon materials. The iron particles proved to be the most promising catalysts for the reduction of bromate into bromide, the highest removal being obtained with the CFeO@CVD750 sample, resulting in a 99% conversion after 120 min of reaction under the conditions tested. Due to its magnetic nature, the catalytic material was easily removed after the reaction and applied in four consecutive cycles without losing its catalytic properties. These results highlight the great potential of carbon-coated magnetic nanoparticles for reducing bromate in water.

The use of magnetic nanoparticles has greatly expanded for numerous biomedical applications over the past two decades due to their high surface area, size-dependent superparamagnetic properties, precision tunability, and easy surface modification. Magnetic nanoparticles can be engineered and manipulated with other nanoparticles and functional compounds to form multi-modal systems useful in theragnosis. However, superior biocompatibility, high loading efficacy, regulated drug release, and in vitro and in vivo stability are necessary for the efficient incorporation of these nanoparticles into physiological systems. In recent years, considerable advancements have been made and reported both in synthesis and application, given the broad range of biomedical-related prospective uses of magnetic nanoparticles. Here, in this review, we have highlighted some essential works, specifically related to the application of magnetic nanoparticles in drug delivery, magnetic hyperthermia, magnetic resonance imaging, magnetic particle imaging, biosensors, and tissue engineering.

We developed extremely small functionalized magnetic nanoparticles (MNPs) for use as an in vivo delivery system for pharmaceuticals and biomolecules. We functionalized the MNPs (d = 3 nm) by silanization of amino groups on the particles with (3-aminopropyl)triethoxysilane for subsequent cross-linking with pharmaceuticals and biomolecules. The MNPs were successfully introduced into living cells without any further modification, such as the use of cationic residues, to enhance endocytic internalization. The particles could be incorporated into the subcutaneous tissue of a mouse's ear through the skin of the ear and could be localized by application of an external magnetic field.We also developed a cell-specific delivery system that makes use of MNPs (d = 3 nm) conjugated with folic acid and a coumarin fluorophore for recognition by folate receptors on the cell surface. The modified MNPs were internalized by human pharyngeal cancer cells (KB cells) after an incubation time that was short compared with the time required for internalization of MNPs without folic acid. Cellular recognition of MNPs may lead to the development of other cell-specific delivery systems.These functionalized MNPs are expected to be useful as a new drug delivery tool.

Magnetic nanoparticles (MNPs) have drawn a lot of interest due to their special qualities, which include large surface area, super para magnetism, and ease of functionalization. These qualities make MNPs perfect for use in electronics, biomedicine, and environmental remediation. This article delivers a critical and nuanced overview, integrating diverse perspectives to advance a deeper understanding of MNP synthesis, characterization, and applications. Typical synthesis methods are covered, such as sol-gel, hydrothermal, thermal decomposition, and co-precipitation. This paper also covers important characterization methods for evaluating the structural and magnetic properties of MNPs, including vibrating sample magnetometry (VSM), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The many uses of MNPs in areas such as environmental pollution control, bio-sensing, and biomedicine are also covered. In addition to offering mechanistic insight into the synthesis, functionalization, and use of MNPs, this thorough analysis also describes the limitations and future possibilities.

The use of magnetic nanoparticles (MNPs) to locally increase the temperature at the nanoscale under the remote application of alternating magnetic fields (magnetic particle hyperthermia, MHT) has become an important subject of nanomedicine multidisciplinary research, focusing among other topics on the optimization of the heating performance of MNPs and their assemblies under the effect of the magnetic field. We report experimental data of heat released by MNPs using a wide range of anisometric shapes and their assemblies in different media. We outline a basic theoretical investigation, which assists the interpretation of the experimental data, including the effect of the size, shape and assembly of MNPs on the MNPs' hysteresis loops and the maximum heat delivered. We report heat release data of anisometric MNPs, including nanodisks, spindles (elongated nanoparticles) and nanocubes, analysing, for a given shape, the size dependence. We study the MNPs either acting as individuals or assembled through a magnetic-field-assisted method. Thus, the physical geometrical arrangement of these anisometric particles, the magnetization switching and the heat release (by means of the determination of the specific adsorption rate, SAR values) under the application of AC fields have been analysed and compared in aqueous suspensions and after immobilization in agar matrix mimicking the tumour environment. The different nano-systems were analysed when dispersed at random or in assembled configurations. We report a systematic fall in the SAR for all anisometric MNPs randomly embedded in a viscous environment. However, certain anisometric shapes will have a less marked, an almost total preservation or even an increase in SAR when embedded in a viscous environment with certain orientation, in contrast to the measurements in water solution. Discrepancies between theoretical and experimental values reflect the complexity of the systems due to the interplay of different factors such as size, shape and nanoparticle assembly due to magnetic interactions. We demonstrate that magnetic assembly holds great potential for producing materials with high functional and structural diversity, as we transform our nanoscale building blocks (anisometric MNPs) into a material displaying enhanced SAR properties.