Hyperthermia and photothermal therapy are some of the oldest therapies known, currently used as an anti-cancer therapy where the tumor temperature is increased to kill cancer cells and enhance the effectiveness of other therapies such as radiation or chemotherapy.
Heating protocols can be classified as a function of the temperature applied over the tumor and the treatment duration. In oncology, treatments can be planned to work between 42 and 45 ºC (hyperthermia), and over 45 ºC (thermal ablation) inducing local or systemic heating. Differences between both strategies are based on the patient’s safety, due to the high temperature the whole body is exposed to in systemic treatments. Instead, in the local treatment the heating is released into the tumor to destroy it preventing damages in surrounding tissues.
The term of magnetic hyperthermia is often wrongly used in some publications when referring to magnetic heating experiments, not the clinical therapy. Even though it is widely acceptable within the nanomaterial research community, it is important to mention it.
Magnetic nanoparticles (MNPs) are remarkably interesting for biomedical applications due to their ability to respond to external magnetic fields which allow their remotely manipulation for targeting, cell separation, drug delivery, and of course also as nano-heaters to destroy tumours. The requirements to use MNPs for clinical purposes are their stability in biological environments and their low toxicity, in addition to their appropriate magnetic properties to be remotely activated by an external magnetic field.
The particles most commonly used in clinical applications are the magnetic nanoparticles composed by iron-oxides phases (i.e. Fe3O4 and Fe2O3) and other magnetic ferrites in spinel structures doped with Mn, Co, Ni or Zn.
To improve their biocompatibility, magnetic nanoparticles designed for biomedicine are coated with both organic and inorganic compounds. In addition, these particles can be functionalized with several ligands stabilizing them in biological environments and providing functionality as specific targeting and controlled drug delivery.
Heating can be achieved by different ways as steam, water and radiation (i.e. infrared, electromagnetic, microwaves and ultrasound). Nowadays, magnetic hyperthermia is used as an adjuvant therapy for cancer treatment in some clinical protocols showing a synergic effect with radiotherapy and chemotherapy enhancing their cytotoxic effects.
Magnetic hyperthermia aims to produce the local heating by a magnetically-mediated heating of low-frequency electromagnetic waves, through the power absorption by magnetic nanoparticles. This technique is one of the most important approaches to induce the local heating by low electromagnetic radiation. Some of the challenges are the control of parameters like energy production, selectivity and localization preventing the damage in healthy tissues.
Currently, the number of research teams working on developing magnetic nanoparticles for biomedicine is increasing day by day. And as it’s expected, in some years from now, the number of clinical trials involving the use of nanomaterials will be far greater. With this starting point, a world of possibilities is opened to magnetic hyperthermia and its implementation in oncologic medicine.
Magnetic nanoparticles used as nano-heaters can be activated by an external magnetic field, through the magnetic coupling between the magnetic component of the field and their magnetic moment. Magnetic nanoparticles absorb the energy from this coupling phenomenon, and dissipate it as heat. For these magnetic fields, biological tissues are “transparent” with no significant energy deposition, thus this technique is safe for all living organism.
The heating capacity depends on the magnetic and physicochemical properties of the magnetic nanoparticles. Regarding magnetic properties, the heat is related to dynamic hysteresis losses produced by the relaxation of the single domain nanoparticles magnetic moments. Relaxation process involve two simultaneous mechanisms associated with the relaxation magnetic moment as shown in Image X.
One of them is related to the physical rotation of the MNPs on the surrounding medium such as liquid carrier and tissue. This process is known as Brownian relaxation, and depends on the medium viscosity and hydrodynamic volume. On the other hand, the Néel relaxation depends on the rotation of the atomic magnetic moments within the crystal lattice of the MNPs.
Both mechanisms are independent, even though they occur simultaneously, the faster one is dominant to induce the heating.
Heating of nanomaterials may also be activated by near-infrared (NIR) mediated by metallic nanoparticles (gold, silver, copper) or even semiconducting carbon nanotubes using laser hyperthermia.
As well as magnetic hyperthermia, laser hyperthermia, requires an agent which interacts with light. The photothermic materials are excited with near-infrared (NIR) radiation which has a light range from 650 nm to 1024 nm. A beneficial aspect of this application is that skin, tissues, and haemoglobin present minimal absorbance at the NIR range, especially for radiation with wavelengths ranging from 650 nm to 900 nm.
Consequently, nowadays there is an increasing interest in the research of new hybrid nanoparticles to combine both therapies, magnetic and laser hyperthermia.
Magnetic heating on living organisms is nowadays intensely studied. The exposure of mammalian cells to magnetic heating may induce cellular events that compromise and/or damage the cells, or may induce a controlled drug released. In cancer cells, as it is well known, high temperatures (42-45ºC) also induce necrosis or apoptosis.
Cell functionalization is one of the most important areas of interest for researchers using magnetic heating of nanomaterials. From release to labelling or just biocompatibility, many papers have addressed this task to help save the gap between the pure magnetic material and the bio application.
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