Biomedical Engineering Reference
In-Depth Information
temperatures in excess of 46 °C [80]. Hyperthermia causes cellular inactivation by
inducing and regulating apoptosis, signal transduction and multi- drug resistance.
Additionally, repeatedly heating tissues to hyperthermic temperatures signals the
release of heat shock proteins [81]. Hyperthermia can also boost the effi cacy of
radiotherapy [82, 83] and chemotherapy [84]. Thermal ablation kills cells directly,
by inducing necrosis [85].
There are several different modalities by which hyperthermia is currently
being investigated in the clinics. These include radiofrequency ( RF ) capacitance,
RF probes, microwave radiation, interstitial laser photocoagulation, direct
tumor injection of hot water, and direct hyperthermia [86]. In general, these
methods have not been successful for treating liver cancer because they are
nonspecifi c and have poor targeting abilities as a result of the uncontrollable
homogeneous heat distribution within the tumor, without harming the healthy
tissues [86] .
The concept of magnetically mediated hyperthermia was fi rst proposed by Gil-
christ [87] in 1957. In that study,
- Fe
3
O
4
nanoparticles of 20 - 100 nm diameter
were injected into the submucosa of the instestinal walls of dogs with bowel
cancer. The lymph nodes, where
γ
- Fe
3
O
4
would be expected to accumulate, were
then surgically removed. When an alternating magnetic fi eld at a power of 200-
240 Oersted (Oe) was applied to the resected lymph nodes, they were seen to have
a magnetite uptake of 5 mg g
− 1
, and an increase in temperature of 14 °C after a
3 min period of treatment [87]. In theory, all metallic objects placed in an alternat-
ing magnetic fi eld should be heated up because of hysteresis loss, Neel relaxation,
or induced eddy currents [88]. The presence of magnetic iron should enhance this
temperature increase - hence the remarkable increase in the temperature of the
lymph nodes with metastasis. This is an important fi nding because a temperature
of 43 °C sustained for at least 240 min (hyperthermia), and a temperature attaining
54 °C, are both cytotoxic to cancer cells.
Some two years after their initial studies on
ex vivo
magnetic fl uid hyperthermia,
Gilchrist and coworkers performed a series of successful hyperthermia experi-
ments on the lymph nodes of rats and dogs [89, 90]. Since then, several groups
have attempted to identify the most effective hyperthermia- based treatment.
During the 1960s, the magnetic particles used in such treatments were mostly
liquid silicones [91, 92], ferropolysaccharides [93], and metal fl akes of iron [94],
although the distribution, clearance, and toxicity of these particles were unknown
at that time. In addition, because of the nature of these materials, tumors and
other sites of interest were often heated unevenly. In 1979, Gordon
et al.
[95]
proposed the concept of intracellular hyperthermia, which involves the introduc-
tion of submicron magnetic particles capable of penetrating the cell membrane,
thus enabling magnetic excitation. Such excitation, which resulted from the appli-
cation of an external high-frequency or pulsed electromagnetic fi eld, raised the
temperature of the particles and thereby generated intracellular heat in precise
increments [95]. The technique resulted in the selective thermal destruction of
cancer cells, which were known to be more sensitive to temperatures in excess of
43 °C, but had very little effect on normal cells. Although most particles used in
γ
