Conventional treatments, like surgery, irradiation, chemotherapy, or combinations of them, are often compromised by systemic toxicity due to lack of tumor specificity. Hyperthermia is a promising approach to treat cancer because cancer cells are susceptible to heat, and when raising the temperature to 43 °C for 30 mins or more, the apoptosis of cancer cells can be triggered. One of the technical problems in hyperthermia is to realize a uniform heating, that is, only the tumor site is heated to the required temperature and other areas are not damaged. This problem can be tackled by using magnetic beads (MBs), which can be accumulated only in the tumor region and then heated by external AC magnetic field.
Categories of Hyperthermia
According to the treated region, hyperthermia can be classified into three types:
The first type of hyperthermia is always achieved by using thermal chambers or blankets. As regards to the partial hyperthermia, which is often applied to treat locally advanced cancer by perfusion or microwaves.The local hyperthermia is mainly used for smaller organs.
Heat Generation Mechanisms of Magnetic Hyperthermia
As well know, the interaction of electromagnetic fields and substance generally leads to the generation of heat. Magnetic hyperthermia utilizes the heat generated by the exposure of magnetic beads to an AC magnetic field. The amount of heat generated per unit volume can be calculated by the following equation:
where μ0 is the permeability of free space, f is the frequency, H is the amplitude. From this equation, we can conclude that the calculation principle of heat largely depends on the characteristics of the electromagnetic field, including frequency and amplitude, as well as the matter properties. However, this formula ignores other possible mechanisms for magnetically inductive heating, such as eddy current heating and ferromagnetic resonance, which are of minor relevance in the present context. The MBs used for hyperthermia normally exhibits poor electroconductivity and are much too small to incorporate eddy current loop. Ferromagnetic resonance effects may become relevant, but it only make sense at frequencies far beyond the general frequency.
Parameters Affecting the Heat
| Extrinsic parameters | Intrinsic parameters |
| Magnetic field amplitude | Particle anisotropy |
| Magnetic field frequency | nature of the surface coating |
| Viscosity of the fluid | MBs concentration |
| Size & surface effects of MBs |
Basic Requisites of magnetic beads (MBs) for Hyperthermia
- Surface Modification
One of the most important issues is to improve the chemical stability of MBs and maintain the surface properties for a long time without agglomeration.
- Water Dispersibility and Colloidal Stability
Water dispersibility of the MBs means that they can be spontaneously dispersed in an aqueous media to form thermodynamically stable solution of particles, which could avoid non-specific adsorption of plasma proteins and can be cleared by immune system faster.
- Biocompatibility
Biocompatibility is necessary when applying MBs to hyperthermia in vivo because these materials are required to perform their desired functions in clinical treatment without producing negative side effects in the patient’s body.
Advantages of magnetic beads (MBs)-based Hyperthermia
- the AMF penetration depth higher than any other activation mechanism (light or acoustic waves), allowing it to reach deeper tissues
- administration of MNPs in a wide concentration range may leave itat the tumor site for repeated therapy sessions
- size-driven magnetic properties of MBsdetermining the heating capabilities on the nanoscale
- precise control of size,morphology and surface modification for diverse goals including biocompatibility, providing chemical groups for attaching biomolecules, and minimizing blood proteins adsorption.
Challenges
Although there have been tremendous results in synthesis and in vivo applications, there have been no reports of the successful clinical implications of MBs-based hyperthermia. The challenge is whether to deliver an adequate quantity of magnetic particles to generate enough heat in the target under AC magnetic field conditions that are clinically acceptable. Most of the laboratory and animal model-based studies reported so far are characterized by the use of magnetic field conditions that could not be safely used in a human patient. Apart from that, the calculation of heat loss in biological environment like blood flow and tissue perfusion is complicated but needs to be solved. After overcoming these limitations,,this technology can make more benefits to cancer patients.
References
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