Magnetic-targeted carrier

Last updated

Magnetic-targeted carriers, also known as MTCs or magnetic vehicles, are micro- or nanoparticles that carry an anticancer drug to the target site by using an external magnetic field and field gradient to direct the desired drug. Usually the complex involves microscopic beads of activated carbon, which bind the anticancer drug. A magnet applied from outside the body then can direct the drug to the tumor site. This can keep a larger dose of the drug at the tumor site for a longer period of time, and help protect healthy tissue from the side effects of chemotherapy. [1]

Magnet material or object that produces a magnetic field

A magnet is a material or object that produces a magnetic field. This magnetic field is invisible but is responsible for the most notable property of a magnet: a force that pulls on other ferromagnetic materials, such as iron, and attracts or repels other magnets.

Contents


Composition and characteristics

The use of MTCs as therapeutic agents for oncology treatment has been increasing exponentially over the past decade. Currently the magnetic vehicle composition relies on the properties of the magnetic component, which is usually ferromagnetic, ferrimagnetic or superparamagnetic, owing to their ability of expressing strong magnetization in the same direction of the external magnetic field while also retaining their magnetization once the external magnetic field is removed. [1]


Magnetic vehicles have been focusing on the particle size, aiming to have the MTCs in the nanoscale, which is mainly due to the fact that ferromagnetic and ferrimagnetic materials show remnant magnetization with and without the external magnetic field, which in turn causes particle aggregation complications. Very small nanoparticles exhibit superparamagnetic properties, which are able to obtain a high degree of magnetization while being able to avoid the particle aggregation issue caused by remnant magnetization. Iron oxide is a common metal used for this purpose, which is usually used as magnetite, maghemite or a combination of the two, due to their high magnetization values between the different iron oxides. Iron oxide gives the impression of lacking remnant magnetization even though magnetite and maghemite are ferromagnetic due to thermal fluctuations, which mostly accounts for the internal interactions of the particles affecting energy densities. [1] [2]


MTCs carry the drug molecules to the tumor site by either having them bound to the surface or by being enclosed within the magnetic vehicle, which can be referred to as the MTC-drug complex. Magnetic-targeted carriers possess unique intrinsic properties, developing magnetic polarization and magnetophoretic mobility once the external magnetic field and field gradient are applied. Selective application of the magnetic field gradient is applied to the target area, which in turn guides the MTC-drug complex to the desired location with a relatively high degree of accuracy, minimum surgical intervention and maximum dose. In order to be able to successfully deliver the drug at the desired tumor location, the magnetic vehicles are responsive to a specific tumor signal, which is commonly a temp- or pH-sensitive release due to the higher temperature and lower pH observed in tumor microenvironments, relative to the rest of the body. [1] [2]

Site-specific targeting requirements

Different requirements exist for magnetic nanoparticles involved in site-specific targeting, which are dependent on either physical or biological reasons. The nine different main requirements the magnetic-targeted carrier should possess are the following: 1) Sufficient magnetic moment to overcome drag and yield forces. 2) Superparamagnetism to prevent agglomeration and embolism. 3) Biocompatibility to prevent toxicity, enhance cell survival and reduce inflammatory responses. 4) Biodegradability to improve clearance from the body. 5) Capability to act as a carrier and exhibit controlled sustained release. 6) Structural stability to allow delivery of therapeutic agents after reaching target site. 7) Stealth and functional surface characteristics to prolong the circulation half-life, improve colloidal stability, prevent agglomerations and reduce toxicity. 8) Reproducible sizes and shapes for clinical applications 9) Reproducible and scalable methods to allow mass production. [1]


Clinical Applications

The most common current clinical application involving a MTC-drug complex is the doxorubicin-magnetic targeted carrier complex, which is composed of a formulation of the anthracycline antibiotic doxorubicin and is bound to microscopic beads of activated carbon. Iron is used as the magnetic-targeted carrier. [1]

History

Magnetic vehicles started being used for drug delivery purposes of chemotherapeutic agents around 1960-1970. MTCs composition has varied over the years and differed between in-vitro and in-vivo studies. Dr. Widder synthesized albumin microspheres in the 1970s encasing Adriamycin, a chemotherapeutic drug, and used magnetite as the susceptible magnetic component to the external magnetic field. One of the first in vivo experiments using magnetic vehicles performed in humans was done by John F. Alksne and his associates in the 1960s, using carbon-coated iron and applied an external magnetic field in order to occlude intracranial aneurysms, which was considered a successful therapeutic once the X-ray results were analyzed. Currently, magnetic nanoparticles, such as iron oxide, take advantage of their multimodality since they can integrate various functionalities, such as imaging agents, targeted-delivery and induce hyperthermia. In addition, iron oxide nanoparticles are being tested in emerging medical fields, such as multimodal imaging, theranostics and image-guided therapies. [1] [2] [3] [4]

Related Research Articles

Ferromagnetism physical phenomenon

Ferromagnetism is the basic mechanism by which certain materials form permanent magnets, or are attracted to magnets. In physics, several different types of magnetism are distinguished. Ferromagnetism is the strongest type and is responsible for the common phenomena of magnetism in magnets encountered in everyday life. Substances respond weakly to magnetic fields with three other types of magnetism—paramagnetism, diamagnetism, and antiferromagnetism—but the forces are usually so weak that they can only be detected by sensitive instruments in a laboratory. An everyday example of ferromagnetism is a refrigerator magnet used to hold notes on a refrigerator door. The attraction between a magnet and ferromagnetic material is "the quality of magnetism first apparent to the ancient world, and to us today".

Nanomedicine the medical application of nanotechnology

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.

Superparamagnetism is a form of magnetism which appears in small ferromagnetic or ferrimagnetic nanoparticles. In sufficiently small nanoparticles, magnetization can randomly flip direction under the influence of temperature. The typical time between two flips is called the Néel relaxation time. In the absence of an external magnetic field, when the time used to measure the magnetization of the nanoparticles is much longer than the Néel relaxation time, their magnetization appears to be in average zero; they are said to be in the superparamagnetic state. In this state, an external magnetic field is able to magnetize the nanoparticles, similarly to a paramagnet. However, their magnetic susceptibility is much larger than that of paramagnets.

Antiferromagnetism magnetic ordering

In materials that exhibit antiferromagnetism, the magnetic moments of atoms or molecules, usually related to the spins of electrons, align in a regular pattern with neighboring spins pointing in opposite directions. This is, like ferromagnetism and ferrimagnetism, a manifestation of ordered magnetism.

Ferrimagnetism Type of magnetic phenomenon

In physics, a ferrimagnetic material is one that has populations of atoms with opposing magnetic moments, as in antiferromagnetism; however, in ferrimagnetic materials, the opposing moments are unequal and a spontaneous magnetization remains. This happens when the populations consist of different materials or ions (such as Fe2+ and Fe3+).

Magnetite iron ore mineral

Magnetite is a rock mineral and one of the main iron ores, with the chemical formula Fe3O4. It is one of the oxides of iron, and is ferrimagnetic; it is attracted to a magnet and can be magnetized to become a permanent magnet itself. It is the most magnetic of all the naturally-occurring minerals on Earth. Naturally-magnetized pieces of magnetite, called lodestone, will attract small pieces of iron, which is how ancient peoples first discovered the property of magnetism. Today it is mined as iron ore.

Ferrofluid

A ferrofluid is a liquid that becomes strongly magnetized in the presence of a magnetic field. A grinding process for ferrofluid was invented in 1963 by NASA's Steve Papell as a liquid rocket fuel that could be drawn toward a pump inlet in a weightless environment by applying a magnetic field. The name ferrofluid was introduced, the process improved, more highly magnetic liquids synthesized, additional carrier liquids discovered, and the physical chemistry elucidated by R. E. Rosensweig and colleagues; in addition Rosensweig evolved a new branch of fluid mechanics termed ferrohydrodynamics.

Maghemite spinel, oxide mineral

Maghemite (Fe2O3, γ-Fe2O3) is a member of the family of iron oxides. It has the same spinel ferrite structure as magnetite and is also ferrimagnetic.

Iron(II,III) oxide chemical compound

Iron(II,III) oxide is the chemical compound with formula Fe3O4. It occurs in nature as the mineral magnetite. It is one of a number of iron oxides, the others being iron(II) oxide (FeO), which is rare, and iron(III) oxide (Fe2O3) also known as hematite. It contains both Fe2+ and Fe3+ ions and is sometimes formulated as FeO ∙ Fe2O3. This iron oxide is encountered in the laboratory as a black powder. It exhibits permanent magnetism and is ferrimagnetic, but is sometimes incorrectly described as ferromagnetic. Its most extensive use is as a black pigment. For this purpose, it is synthesised rather than being extracted from the naturally occurring mineral as the particle size and shape can be varied by the method of production.

Ferrite (magnet) ceramic materials, many of them magnetic

A ferrite is a ceramic material made by mixing and firing large proportions of iron(III) oxide (Fe2O3, rust) blended with small proportions of one or more additional metallic elements, such as barium, manganese, nickel, and zinc. They are both electrically non-conductive, meaning that they are insulators, and ferrimagnetic, meaning they can easily be magnetized or attracted to a magnet. Ferrites can be divided into two families based on their resistance to being demagnetized (magnetic coercivity).

Superferromagnetism is the magnetism of an ensemble of magnetically interacting super-moment-bearing material particles that would be superparamagnetic if they were not interacting. Nanoparticles of iron oxides, such as ferrihydrite, often cluster and interact magnetically. These interactions change the magnetic behaviours of the nanoparticles and lead to an ordered low-temperature phase with non-randomly oriented particle super-moments.

Molecule-based magnets are a class of materials capable of displaying ferromagnetism and other more complex magnetic phenomena. This class expands the materials properties typically associated with magnets to include low density, transparency, electrical insulation, and low-temperature fabrication, as well as combine magnetic ordering with other properties such as photoresponsiveness. Essentially all of the common magnetic phenomena associated with conventional transition-metal and rare-earth-based magnets can be found in molecule-based magnets.

Magnetic nanoparticles are a class of nanoparticle that can be manipulated using magnetic fields. Such particles commonly consist of two components, a magnetic material, often iron, nickel and cobalt, and a chemical component that has functionality. While nanoparticles are smaller than 1 micrometer in diameter, the larger microbeads are 0.5–500 micrometer in diameter. Magnetic nanoparticle clusters that are composed of a number of individual magnetic nanoparticles are known as magnetic nanobeads with a diameter of 50–200 nanometers. Magnetic nanoparticle clusters are a basis for their further magnetic assembly into magnetic nanochains. The magnetic nanoparticles have been the focus of much research recently because they possess attractive properties which could see potential use in catalysis including nanomaterial-based catalysts, biomedicine and tissue specific targeting, magnetically tunable colloidal photonic crystals, microfluidics, magnetic resonance imaging, magnetic particle imaging, data storage, environmental remediation, nanofluids,, optical filters, defect sensor, magnetic cooling and cation sensors.

Iron oxide nanoparticles are iron oxide particles with diameters between about 1 and 100 nanometers. The two main forms are magnetite (Fe3O4) and its oxidized form maghemite (γ-Fe2O3). They have attracted extensive interest due to their superparamagnetic properties and their potential applications in many fields (although Co and Ni are also highly magnetic materials, they are toxic and easily oxidized).

Single domain, in magnetism, refers to the state of a ferromagnet in which the magnetization does not vary across the magnet. A magnetic particle that stays in a single domain state for all magnetic fields is called a single domain particle. Such particles are very small. They are also very important in a lot of applications because they have a high coercivity. They are the main source of hardness in hard magnets, the carriers of magnetic storage in tape drives, and the best recorders of the ancient Earth's magnetic field.

Néel relaxation theory is a theory developed by Louis Néel in 1949 to explain time-dependent magnetic phenomena known as magnetic viscosity. It is also called Néel-Arrhenius theory, after the Arrhenius equation, and Néel-Brown theory after a more rigorous derivation by William Fuller Brown, Jr. Néel used his theory to develop a model of thermoremanent magnetization in single-domain ferromagnetic minerals that explained how these minerals could reliably record the geomagnetic field. He also modeled frequency-dependent susceptibility and alternating field demagnetization.

A nanocarrier is nanomaterial being used as a transport module for another substance, such as a drug. Commonly used nanocarriers include micelles, polymers, carbon-based materials, liposomes and other substances. Nanocarriers are currently being studied for their use in drug delivery and their unique characteristics demonstrate potential use in chemotherapy.

Magnetic nanoparticle-based drug delivery is a means in which magnetic particles such as iron oxide nanoparticles are a component of a delivery vehicle for magnetic drug delivery, due to their easiness and simplicity with magnet-guidance. Magnetic nanoparticles can impart imaging and controlled release capabilities to drug delivery materials such as micelles, liposomes, and polymers.

Superparamagnetic relaxometry (SPMR) is a technology combining the use of sensitive magnetic sensors and the superparamagnetic properties of magnetite nanoparticles (NP). For NP of a sufficiently small size, on the order of tens of nanometers (nm), the NP exhibit paramagnetic properties, i.e., they have little or no magnetic moment. When they are exposed to a small external magnetic field, on the order of a few millitesla (mT), the NP align with that field and exhibit ferromagnetic properties with large magnetic moments. Following removal of the magnetizing field, the NP slowly become thermalized, decaying with a distinct time constant from the ferromagnetic state back to the paramagnetic state. This time constant depends strongly upon the NP diameter and whether they are unbound or bound to an external surface such as a cell. Measurement of this decaying magnetic field is typically done by Superconducting Quantum Interference Detectors (SQUIDs). The magnitude of the field during the decay process, determines the magnetic moment of the NPs in the source. A spatial contour map of the field distribution determines the location of the source in three dimensions as well as the magnetic moment.

Magnetoelastic filaments are one-dimensional composite structures that exhibit both magnetic and elastic properties. Interest in these materials tends to focus on the ability to precisely control mechanical events using an external magnetic field. Like piezoelectricity materials, they can be used as actuators, but do not need to be physically connected to a power source. The conformations adopted by magnetoelastic filaments are dictated by the competition between its elastic and magnetic properties.

References

  1. 1 2 3 4 5 6 7 Polyak B, Friedman G (2009-01-01). "Magnetic targeting for site-specific drug delivery: applications and clinical potential". Expert Opinion on Drug Delivery. 6 (1): 53–70. doi:10.1517/17425240802662795. PMID   19236208.
  2. 1 2 3 Alexiou C, Jurgons R, Seliger C, Brunke O, Iro H, Odenbach S (2007-07-01). "Delivery of superparamagnetic nanoparticles for local chemotherapy after intraarterial infusion and magnetic drug targeting". Anticancer Research. 27 (4A): 2019–202. PMID   17649815.
  3. Bao G, Mitragotri S, Tong S (2013-07-11). "Multifunctional nanoparticles for drug delivery and molecular imaging". Annual Review of Biomedical Engineering. 15: 253–282. doi:10.1146/annurev-bioeng-071812-152409. PMC   6186172 . PMID   23642243.
  4. Goodwin S, Peterson C, Hoh C, Bittner C (1999-04-01). "Targeting and retention of magnetic targeted carriers (MTCs) enhancing intra-arterial chemotherapy". Journal of Magnetism and Magnetic Materials. 194 (1–3): 132–139. Bibcode:1999JMMM..194..132G. doi:10.1016/S0304-8853(98)00584-8.


PD-icon.svg This article incorporates  public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms" .