Overview Magnetic Nanoparticles (MNPs) are new and rapidly emerging applications in recent years, in many fields of modern science such as biomedicine, magnetic fluids, catalysis, magnetic resonance imaging, data storage and Environmental protection and other applications are becoming more and more widely used. Magnetic nanoparticles have a unique and superior physical and chemical properties. With the development of synthetic technology, a series of magnetic nanoparticles with controllable shape, good stability and monodispersion have been successfully produced. The application of magnetic nanoparticles in biomedicine mainly falls into two categories: in vitro applications include separation and purification, magnetic transfection, immunoassay, catalysis, Magnetorelaxometry, and solid phase extraction. In vivo applications can be broadly divided into therapeutic and diagnostic applications, such as hyperthermia and magnetic targeting drugs, and diagnostic applications such as Nuclear Magentic Resonance (NMR). Biological separation and purification is one of the most important technologies in biological and pharmaceutical technology. This is also the most fruitful of the magnetic particle applications. The magnetic separation method has the advantages of high efficiency, simplicity, and speed. Magnetic particles can be used for the separation of biomolecules and cells such as proteins and nucleic acids. The separation and purification of nucleic acids is performed using nano-sized magnetic particles. The two main properties of magnetic nanoparticles that affect in vivo applications are size and surface function. The diameter of Superparamagnetic Iron Oxide (SPIOs) has a great influence on their biodistribution in the body. Particles with a diameter of 10-40 nm, including ultra-small superparamagnetic iron oxide nanoparticles, can remain in the blood circulation for a long time, they can pass through the capillary wall and are often swallowed by macrophages that go to the lymph nodes and bone marrow. Linaclotide,Teriparatide Acetate,Leuprorelin Acetate,Lypressin Acetate PYSON Co. ,Ltd. , https://www.pysonbio.com
With the joint efforts of scientists, engineers, chemists and physicists, nanotechnology has made great progress at the molecular and cellular levels in the life sciences and health care fields. Magnetic nanoparticles are nano-sized particles, generally composed of a magnetic core composed of a metal oxide such as iron, cobalt, or nickel, and a high molecular polymer/silicon/hydroxyapatite shell layer wrapped around a magnetic core. The most common core layer is made of Fe3O4 or γ-Fe2O3 with superparamagnetic or ferromagnetic properties. It has magnetic orientation (targeting). Under the action of external magnetic field, it can realize directional movement, convenient positioning and separation from medium. . The most common shell layer consists of a high molecular polymer, and the reactive groups coupled to the shell layer can be combined with various biomolecules, such as proteins, enzymes, antigens, antibodies, nucleic acids, etc., to achieve their functionalization. Therefore, the magnetic nanoparticles have the characteristics of magnetic particles and polymer particles, and have magnetic guiding properties, biocompatibility, small size effects, surface effects, active groups, and certain biomedical functions.
Due to its unique physical and chemical properties, magnetic nanoparticles can simplify the cumbersome and complicated traditional experimental methods and shorten the experimental time. It is a new type of high-efficiency reagent. At present, magnetic nanoparticles are mainly used in biomedicine for magnetic separation, magnetic transfection, nucleic acid/protein/virus/bacteria detection, immunoassay, magnetic drug targeting, tumor hyperthermia, magnetic resonance imaging and sensors. The properties of magnetic nanoparticles and their main applications in the biomedical field are described in detail below, and specific products corresponding to different applications are listed.
Properties of magnetic nanoparticles
The magnetic properties of the magnetic nanoparticles make them easy to enrich and separate, or to perform directional movement positioning. The magnetic effect is formed by the movement of particles of mass and charge. These particles include electrons, protons, positively and negatively charged ions, and the like. Rotation of charged particles produces a magnetic dipole, a magnet. The magnetic domain refers to all the magnetons in a volume of ferromagnetic material arranged in the same direction under the action of exchange force. This concept distinguishes ferromagnetic from paramagnetic.
Ferromagnetic materials have a spontaneous magnetization and are magnetic when there is no external magnetic field. The magnetic domain structure of the ferromagnetic material determines the dependence of the magnetic behavior on the size. When the volume of the ferromagnetic material is below a certain critical value, it becomes a single magnetic domain. This critical value is related to the intrinsic properties of the material, typically around tens of nanometers. The magnetic properties of very small particles are derived from the size effect based on the magnetic domain structure of the ferromagnetic material. The conclusion of this conclusion is that ferromagnetic particles have a uniform magnetic property for particles smaller than a certain critical value and a non-uniform magnetic property for larger particles in a state with the lowest free energy. The former smaller particles are referred to as single magnetic domain particles, and the latter larger particles are referred to as multi-domain particles.
When the diameter of the single magnetic domain particles is further lowered than the critical value, the coercive force becomes zero, and such particles become superparamagnetic. Superparamagnetic is caused by thermal effects. Superparamagnetic nanoparticles are magnetic under the action of an external magnetic field and do not have magnetism after removal of the applied magnetic field. In living organisms, superparamagnetic particles are magnetic only when there is an applied magnetic field, which makes them uniquely advantageous in an in vivo environment. Crystal materials such as iron, cobalt, and nickel all have ferromagnetism, but since iron oxide magnets (Fe3O4) are the most magnetically natural minerals on the earth and have high biosafety (cobalt and nickel materials are biologically toxic), In many biomedical applications, superparamagnetic forms of iron oxide magnetic nanoparticles are most common.
Ferrofluid (magnetic fluid) is a liquid that becomes very magnetic under the action of an external magnetic field. It is a new functional material that is both magnetic and fluid. The ferrofluid is a colloidal solution composed of nanoscale ferromagnetic or ferrimagnetic, and the particles are suspended in a carrier solution, which is usually an organic solvent or water. The nanoparticles are completely encapsulated by a surfactant to prevent polymerization into agglomerates. Ferrofluids are generally classified as superparamagnetic when they are not magnetically held without an applied magnetic field. Nanoparticles in ferrofluids do not settle under normal conditions due to thermal motion.
The specific surface area (surface area to volume ratio) of the magnetic nanoparticles of the spherical particles is inversely proportional to the diameter. For particles smaller than 0.1 um in diameter, the percentage of surface atoms increases sharply, and the surface effect is remarkable. The particle diameter is reduced, the specific surface area is significantly increased, and the number of surface atoms is rapidly increased. When the particle size is 1 nm, the number of surface atoms is 99% of the total number of complete crystal atoms. At this time, almost all the atoms constituting the nanoparticles are distributed on the surface, and many dangling bonds are formed around the surface atoms, which have unsaturation and are easy to Other atoms combine to form a stable structure and exhibit high chemical activity. Therefore, the target molecule/atom is highly efficient.
Magnetic nanoparticles have good biocompatibility with various polymers. The surface modification of magnetic nanoparticles includes: non-polymer organic fixation, polymer organic fixation, inorganic molecular immobilization, and targeted modification. Commonly used as a modification are polyethylene glycol, dextran, polyvinylpyrrolidone, fatty acid, polyvinyl alcohol, polypeptide, gelatin, chitosan, methylsilane, liposome and the like. There are two main ways to modify the surface of magnetic nanoparticles: one is that the surface modification material and the surface of the particle rely on chemical bonding, which usually refers to some organic small molecular compounds; the second is to directly encapsulate the magnetic nanoparticles with organic or inorganic materials, mainly including the surface. Active agents, high molecular polymers, precious metals, and silica. Surface modification not only enhances the stability of magnetic nanoparticles, but also improves its dispersibility and biocompatibility in aqueous solution, improves targeting, prevents protein adsorption, increases its time in the blood circulation, and further recombines other Nanoparticles, compounds or biological ligands to achieve functionalization of magnetic nanoparticles.
Application of magnetic nanoparticles
In vitro application:
In biological separation, magnetic nanoparticles have small volume, large surface area, good dispersibility, and can quickly and effectively bind biomolecules, and this combination is reversible, and the formation of flocs can be controlled, thus using magnetic nanoparticles for separation. It is superior to the traditional method of using micron-sized resins and beads. Most of the magnetic nanoparticles used for separation are superparamagnetic - in the absence of an applied magnetic field, the particles are non-magnetic and uniformly suspended in the solution, and when an applied magnetic field is used, the particles are magnetically separable. Active substances such as bioactive adsorbents or other ligands attached to the surface of the magnetic nanoparticles can specifically bind to specific biomolecules or cells and be separated by an external magnetic field. The magnetic separation method basically comprises only two steps: 1. labeling the target molecule or cell with magnetic nanoparticles; 2. separating the target molecule or cell by a magnetic separation device. One example of the separation of magnetic nanoparticles is the combination of specific antibodies and magnetic nanoparticles, which can be attached to specific cells, and the magnetic field can be quickly separated or immunologically analyzed by applying a magnetic field. Such a method has high specificity, rapid separation, and good reproducibility. For another example, the glucose-DEAE is coated on the surface of the magnetic nanoparticles, and the plasmid is purified in the bacterial lysis supernatant by ion exchange using charge adsorption between the positively charged DEAE and the negatively charged nucleic acid.
Magneticofection is a method of transfecting magnetic nanoparticles combined with carrier DNA into cells under the influence of an external magnetic field. The magnetic particles used for magnetic transfection are mostly surface-modified with polycationic or polyaziridine. Because of their positive charge, they are easy to bind to negatively charged DNA, and the transfection efficiency is increased by tens to thousands of times compared to transfection with viral or non-viral vectors. Magnetic transfection also has improved transgene expression, and the use of very low dose vectors can achieve both high transfection efficiency and high transgene expression, and is simple to use. Magnetic transfection methods have been successfully used in many types of adherent cells and a few suspension cells, including primary cells, tumor cells, etc., which are difficult to transfect with conventional methods. The MagnetofectionTM magnetic transfection reagent produced by Chemicell in Germany has been selected by many of the world's top laboratories and has published many articles.
Immunoassay is an important method in modern bioanalytical techniques that allows the quantitative analysis of proteins, antigens, antibodies and cells. For example, in immunoassay, antibodies (or antigens) are often labeled with labels with special physicochemical properties such as radioisotopes, enzymes, colloidal gold and organic fluorescent dye molecules, and after antigen and antibody recognition, The purpose of detecting the antigen (or antibody) is achieved by qualitative or quantitative detection of the label. Since the magnetic nanoparticles have superparamagnetism, it provides great convenience for separation, enrichment and purification of samples, and has attracted extensive attention in immunoassay.
In recent years, supporters using magnetic nanoparticles have been widely used to improve the problem of catastrophic heterogeneity. Magnetic separation makes it easier to recover the catalyst in a liquid phase reaction than with a cross-flow filtration and centrifugation process, especially when the catalyst is in the submicron range. The catalyst which is so small and magnetically separable has the advantages of high dispersibility and reactivity and easy separation. The immobilization of these active materials with magnetic nanoparticles makes it easy to separate the catalyst in a quasi-homogeneous system in terms of recycling expensive catalysts or ligands. In recent years, different types of transition metal catalyzed reactions have been carried out by grafting catalytic sites onto magnetic nanoparticles, including carbon-carbon crosslinking reaction, olefin hydroformylation reaction, hydrogenation, polymerization reaction and the like. Catalysts supported by magnetic nanoparticles have been reported to include enzymes, amino acids that hydrolyze esters, organic amine catalysts that promote Knoevenagel reactions and related reactions, and the like.
Magnetorelaxometry (MRX) technology detects magnetic viscosity – the net magnetic moment of a magnetic nanoparticle system after removal of a magnetic field. There are two different relaxation mechanisms: Neil relaxation and Brownian relaxation, the difference between the two mechanisms is the relaxation time. In addition, Brownian relaxation occurs only in liquids, whereas Neil relaxation does not depend on the dispersion of nanoparticles. The phenomenon that Magnetorelaxometry is determined by nuclear size, hydration diameter, and anisotropy allows this technique to be used to distinguish whether the state is free or bound based on the magnetic behavior of the free and bound conjugates, so this technique can be used as an assessment of immunoassays. analyzing tool.
Magnetorelaxometry was originally used to evaluate immunoassays, which can be used for in vitro or in vivo studies. Magnetorelaxometry can quantitatively analyze the distribution of magnetic nanoparticles in organs or whole animals. Since this method is non-invasive, animals can be monitored for a long time, such as monitoring magnetically labeled stem cells. Another example is cancer diagnosis. Magnetic Relaxation Immunoassay (MARA) using functionalized magnetic nanoparticles in recent years is based on this physics method. The advantage of magnetic relaxation immunoassay is that the combined particles and free particles produce different signals. Unlike traditional methods, no washing step is required; no markers are required; each detection time is extremely short, so it can be used for high throughput. Experiment; magnetic relaxation can be used for in vivo experiments because it can be detected in an opaque medium; magnetic nanoparticles are combined with techniques based on high sensitivity magnetic field sensors such as SQUID (Superconductive Quantum Interference Device) for detecting magnetic relaxation. , high sensitivity can be obtained. In this application, as with separation and purification, nanoscale particles are also superior to micron particles.
At present, Solid-Phase Extraction (SPE) has received much attention as a target for separation and preconcentration of components from samples. Solid phase extraction is a common method for detecting trace contaminants from environmental samples. Recently, the application of nanoscale particles in sample extraction has been rapidly and rapidly developed. Solid phase extraction is a good alternative to traditional sample enrichment methods such as liquid phase extraction. The solid phase extraction method using a standard purification column is very time consuming when separating and preconcentrating the target component from a large volume of sample. Therefore, Magnetic Solid-Phase Extract (MSPE) using magnetic or magnetizable adsorbents is becoming more and more important. In this process, a magnetic adsorbent is added to the solution or suspension containing the target component. Then, the magnetic adsorbent to which the target component is adsorbed is recovered by a suitable magnetic separation device.
In environmental science, studies on the removal of organic and inorganic contaminants using magnetic nanoparticles have been conducted in recent years, and experiments to remove contaminants from groundwater, soil and air have been used on a laboratory and field scale. Most of the high concentrations of organic pollutants are dyes. Dyes in dyeing and dyeing factories, pigment factories, tanneries, etc. all contain dyes. Replacing expensive or inefficient adsorbents with magnetic nanoparticles can be a good platform, but more research is needed. A major aspect of the removal of inorganic contaminants is the removal of metal toxins. Magnetic nanoparticles, as a sorbent for removing metal toxins from complex matrices, have the advantages of high capacity and high efficiency, and are smaller in size and larger in surface area than micron-sized sorbents. These findings have helped to design better adsorption treatment plans to remove or recover metal ions from wastewater. In addition, functionalized magnetic nanoparticles can be used to separate and detect microorganisms such as bacteria and fungi in environmental samples.
In vivo application:
Hyperthermia refers to the placement of superparamagnetic iron oxide in an alternating electromagnetic field, which allows the magnetic direction to be randomly transformed between parallel and antiparallel, so that the magnetic energy is transferred to the particles in the form of heat, which can be used to destroy diseased cells in the living body. . Tumor cells are more sensitive to temperature than healthy cells. Studies have shown that magnetic cationic liposome nanoparticles and dextran-encapsulated magnets effectively increase the temperature of tumor cells in hyperthermia of cell radiation. This approach is considered to be the primary method of future cancer treatment. The advantage of magnetic hyperthermia is that the temperature rise is limited to the tumor area. In addition, subdomain magnetic particles (nanoscale) are superior to multidomain magnetic particles (micron) because they absorb more energy in the AC magnetic field that the body can withstand, depending on their size and shape. Therefore, a clear synthetic route that produces uniform particles is critical to tight temperature control.
Drug targeting has become one of the modern drug delivery technologies. The magnetic nanoparticles and the applied magnetic field and/or the magnetizable implant can deliver the particles to the target region, immobilizing the particles at a local site upon release of the drug, and thus the drug can be released locally. This process is called Magnetic Drug Targeting (MDT). Recently, the feasibility of using iron oxide magnetic nanoparticles for targeted administration is increasing. The magnetic nanoparticles using Fe3O4 in the core have small diameter, high sensitivity, low toxicity, stable performance, and easy availability of raw materials. Fe3O4 generally does not produce toxic side effects to the human body. The carrier containing iron for the whole course of treatment does not exceed the total amount of iron supplemented by anemia patients. Except for some of the body's use, the remaining magnetic particles can be safely excreted through the skin, bile, kidneys, etc. . Nanoparticle surface modified organic polymers or inorganic metals or oxides make them biocompatible and suitable for attachment to biologically active molecules for functionality. Delivery of the drug to a particular site eliminates the side effects of the drug and reduces the amount of drug used.
The application of magnetic nanoparticles in in vivo diagnostics is mainly used for nuclear magnetic resonance imaging. Due to the development of diagnostic imaging of magnetic resonance imaging, a new class of drugs, magnetic drugs, has emerged. The main use of these drugs after administration to patients is to increase the contrast (contrast) of normal and diseased tissues and/or to show organ function or blood flow. Superparamagnetic iron oxide nanoparticles become a new class of probes in cell and molecular imaging in vitro and in vivo. The use of superparamagnetic developers in nuclear magnetic resonance has the advantage of producing stronger proton relaxation than paramagnetic developers. Thus, there is less need for a developer to be injected into the body. However, NMR is not convenient for in situ monitoring.
Magnetic nanoparticles have shown unique advantages in the biomedical field, and their application in this field is still growing rapidly. Magnetic nanoparticles will play a greater role in the biomedical field and other fields.
Chemicell, Germany, produces a variety of magnetic nanoparticles, magnetic nanoparticles, fluorescent nanoparticles, fluorescent particles, etc., suitable for a variety of biomedical applications. Beijing Qiwei Yicheng Technology Co., Ltd. represents all products of Chemicell. Some of the magnetic nanoparticle products and applications of Chemicell are shown in the table below.
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