Thesis - Magnetic Hyperthermia Treatment and Cancer
Magnetic fluid hyperthermia is a promising cancer treatment that essentially ”fries” cells inside tumors. The procedure has been used successfully in prostate, liver, and breast tumors. Magnetic nanoparticles (each billionths of a meter in size) are injected into the body intravenously and diffuse selectively into cancerous tissues. Add a high-frequency magnetic field, and the particles heat up, raising the temperature of the tumor cells.
Thermal transfer plays an important role in many environmental, industrial, and biological processes. The knowledge of heat transfer can be applied to our everyday life, e.g., electrical power generation, energy conversion and storage, combustion processes, thermal insulation, refrigeration, material processing, and biological systems. A heat transfer analysis typically provides the rates of heat transfer and/or the temperature distributions for steady or transient states for specified boundary conditions, initial conditions, geometries, and materials. The transfer of heat in a stationary medium such as a solid, a liquid, or a gas is called heat conduction, but when the medium moved there is heat convection.
Temperature is a key factor in the normal biological development of the stem cell, determining the sex of an amphibian, and developing immune therapies . The human body has the ability to increase its basal temperature to fight diseases. When the body is infected by viruses and bacteria, it instinctively defends itself by increasing its temperature to slow or halt the rapid growth of the pathogens. It leads to what we call fever, which is another form of hyperthermia, i.e., by elevating in body temperature for therapeutic reasons. The normal body naturally maintains a temperature of 37 ◦C, and healthy cells can survive up to 42 ◦C. The elevation of body temperature enhances host defense. For this reason, thermal therapy is useful in clinical applications, such as the treatment of cancer. It is another way to induce therapy by elevating the temperature to a therapeutic temperature range of 42-45 ◦C to kill cancerous cells.
Thermal stress leads to the denaturation of proteins within cells which causes cell damage . Thermally induced stress proteins or heat shock proteins (HSP) were described about forty years ago. HSP occurs when temperatures are elevated in the nonlethal regions of tumor to help refold and repair denatured proteins. It synthesizes new proteins by inducing a wide variety of cellular functions and defense, including chaperoning functions. HSP levels can be triggered by environmental stresses (for example chemicals, heat shock, heavy metals), a pathophysiological state (fever, viral infection, inflammation), and non-stressful conditions (cell cycle) . HSPs are reported to be useful to increase the effectiveness of cancer vaccines. Different ranges of body temperatures can induce an immune response against tumors, i.e.,
Fever-range temperature: activities of immune cells
Heat shock temperature: increase of immunogenicity of tumor cells
Cytotoxic temperature: creation of an antigen source for induction of an anti-tumor immune response.
In the fever and heat shock ranges, although the temperature is not high enough to kill cancer cells, it is sufficient to modify the tumor and immune cells. This mild hyperthermia can significantly potentiate the effects of radiotherapy and chemotherapy. Thus, combinations with hyperthermia can lower doses of chemotherapeutic agents or radioactivity, leading to a lower toxicity to achieve a patient effective treatment. In the cytotoxic range, the sustained temperature above 42 ◦C causes necrosis of cancerous cells.
Since hyperthermia can be used in combination with radiotherapy and chemotherapy, one may not need to apply a thermal dose at a cytotoxic level. Also it can be used alone to treat the entire tumor or only specific locations. There are several techniques that have been proposed to achieve the hyperthermia as follows ,
|Whole body hyperthermia||Warm-water blankets, Inductive coils, Thermal chambers|
|Regional hyperthermia||Regional perfusion, Continuous hyperthermia, Peritoneal perfusion|
|Local hyperthermia||Radio waves, Laser ablation, Microwaves, Ultrasound waves|
The above hyperthermia techniques can treat tumors, whereas local hyperthermia (with radio waves, laser ablation, ultrasound waves, microwaves) can be applied externally to treat tumors near the skin and to reach the deep cancerous cells by using probes. However, treatment is also limited by the ability of the hyperthermia source to penetrate body tissues that surround tumors. Care should be taken to not harm the healthy tissues that lie between the external source and the cancer. Temperatures above 42 ◦C in healthy tissues bring discomfort, burns, and blisters. Magnetic fluid hyperthermia (MFH) can help overcome these problems. The thesis points to potential pathways in this regard.
Many studies have outlined the potential of applying iron oxide magnetic nanoparticles for cancer therapy and drug delivery. Some biomedical applications of magnetic fluids include magnetic separation, contrast enhancement of magnetic resonance imaging, drug delivery, and hyperthermia. In 1957, Gilchrist et al.  primarily investigated the use of magnetic materials for hyperthermia. The fine magnetic microparticles were injected into lymphatic channels and heated by hysteresis at radio frequencies. However, the heating mechanism of ferrofluid that is a colloidal suspension of magnetic nanoparticles in a fluid medium is different. An alternating magnetic field is applied to provide the energy to reorient the magnetic moment of a nanoparticle and the geometric orientation of the nanoparticle itself. This magnetic energy is converted into thermal energy due to friction with the surrounding tissues when a nanoparticle rotates through viscous soft matter, which contributes to heating. The two mechanisms for magnetic relaxations in nanoparticles are Brownian (physical rotation of the nanoparticle in the fluid) and N ́eel relaxation (the rotation of its magnetic moment).
For MFH application, biocompatible superparamagnetic (SPM) nanoparticles are infused into a tumor and selectively heated by imposing an AC magnetic field. It elevates the tumor temperature while keeping the surrounding healthy tissue temperature at a normal level [10,11]. Sufficient heat must be generated by the SPM nanoparticles to heat the tumor tissue to at least 42 ◦C over an extended period to reduce the consumption of oxygen and vital nutrients in the cancerous cells leading to tumor death through hyperthermia .
The nanoparticles must have large magnetic moments which make magnetite (Fe3O4) and maghemite (γ-Fe2O3) suitable for MFH applications. It is also desirable to obtain a high specific loss power (SLP) heat generated per unit mass of MNPs. This is strongly dependent on the particle distribution, size, anisotropy constant, surface modification, and saturation magnetization . Thus, materials with larger magnetic anisotropy and larger magnetic moments also produce higher SLP for smaller particle sizes.
There are unresolved issues related to the overheating of healthy tissues surrounding tu- mors, which can consequently be damaged. We perform parametric investigations of MFH treatment to suggest optimal clinical treatment conditions that induce minimal damage to the healthy tissue surrounding a tumor in Chapter 2 . Our analysis characterizes the steady and transient response of a tumor and healthy tissue to MFH in a manner helpful for designing in vitro and in vivo MFH experiments.
For optimal MFH treatment, a minimal dosage should be able to provide sufficient heat- ing which depends on the ferrofluid properties, and the strength and frequency of the AC field. Guidance regarding the influence of both particle size on MFH under typical clinical conditions is provided in in Chapter 3 . There, we describe the appropriate use of magnetic nanoparticles (MNPs) to heat soft tissue using an AC magnetic field. We note that changing the nanoparticle size can significantly alter the ability of an MNP to generate heat. Moreover there should be an optimum particle size for a specified set of conditions.