Cancer is a disease characterized by unregulated growth of cells. This is caused by damage of deoxyribonucleic acid (DNA) results in mutations to vital genes that control cells divisions
The current methods for cancer treatment have moderate to severe secondary effects. For this reason, the investigations of new alternatives are essentially. Thermo-therapy is considered one of the most important methods for cancer treatment. In general, the term thermo-therapy refers to both hyperthermia and thermal ablation therapy(
The thermal therapy can provide a minimal invasive alternative to conventional surgical treatment of solid tumors. In addition, the thermal therapeutic procedures are relatively simple to perform and therefore have the potential to improve recovery times and reduce the complication rates and hospital stays
To overcome these problems, new techniques in the field of nanoscience, nanotechnology and nanomedicine are now developing into treatment approach based on internal heating of tissue such as magnetic fluid hyperthermia (MFH), which in turn based on internal heating sources. In order to achieve the optimal effectiveness, this approach requires photo-thermal convectors to allow heat production within a localized region at lower incident energies. This requires development of particular particles that have highly magnetic properties such as Super-paramagnetic Iron Oxide Nanoparticles Fe3O4 (SPIO NPs). During this approach surrounding healthy cells are capable of surviving exposure to temperatures up to around 46.5°C and more readily able to dissipate heat and maintain a normal temperature while the targeted tumor tissues have a higher thermal sensitivity than normal tissue because of experience difficulty in dissipating heat due to the disorganized and compact vascular structure (reduced blood flow), anaerobic metabolism (acidosis), and nutrient depletion. So an irreversible damage to diseased cells occurs at temperatures in a range from approximately 40°C to about 46°C (Yu-Fen et al., 2008).
2. Nanomedicine and magnetic nanomaterials
Nanomedicine stands at the boundaries between the physical, the chemical, biological and medical sciences. It originated from the imaginative idea that robots and other related machines at the nanometer scale could be designed, fabricated and introduced into the human body for repairing malignant cells at the molecular level. According to its original vision, nanomedicine is a process including the diagnosis, treatment and prevention of diseases and traumatic injuries, and the preservation and improvement of human health, using molecular tools and molecular knowledge of the human body (
2.1. Status of nanomedicine
Nanomedicine has developed in numerous directions, and it has been fully acknowledged that the capability of structuring materials at the molecular scale greatly benefits the research and practice of medicine. However, nanomedicine is a long-term expectation. Before nanomedicine can be used in clinics, fundamental mechanisms of nanomedicine should be fully investigated, and clinical trials and validation procedures should be strictly conducted. Though, it is possible that some biological entities, such as proteins, DNA and other bio-polymers, could be directly used for biosensor applications, nevertheless some serious issues, such as biocompatibility and robustness, may hinder the progress of these efforts. Though in many areas, such as disease diagnosis, targeted drug delivery and molecular imaging, clinical trials of some nanomedicine products are being made, the clinical applications of these techniques, which require rigorous testing and validation procedures, may not be realized in the near future (Royal Society and Royal Academy of Engineering 2004). At all events, it should be noted that although the applications of nanomaterials in biology and medicine are in an embryo stage, it is the great promise of nanomedicine that has inspired researchers to extensively investigate the interfaces between nanotechnology, biology and medicine (
2.2. Magnetic nanomaterials
The magnetic nanomaterials used in biology and medicine generally fall into three categories: zero dimensional nanomaterials such as nanospheres; one-dimensional nanomaterials such as nanowires and nanotubes; and two-dimensional nanomaterials such as thin films. Usually, all the nanospheres, nanorods, nanowires and nanotubes are called nanoparticles, among which, nanorods, nanowires and nanotubes are high aspect-ratio nanoparticles. In most of the biomedical applications, magnetic nanoparticles are suspended in appropriate carrier liquids, forming magnetic fluids, also called ferrofluids. Among the three types of magnetic nanoparticles, magnetic nanospheres are most widely used in biomedicine. To realize their biomedical applications, the magnetic nanospheres should be stably suspended in the carrier liquid, and they should also carry out certain biomedical functions. The magnetic material most often used is iron oxides, and the carrier liquids are usually water, kerosene or various oils. Due to their small size, the magnetic nanoparticles in carrier liquids neither form sediment in the gravitational field or in moderate magnetic field gradients, nor do they agglomerate due to magnetic dipole interaction. However, a stable suspension can only be achieved if the particles are protected against agglomeration due to the van der Waals interaction. Usually this protection can be achieved by one approach is the electric charge stabilization. In this approach, a thin layer of gold is coated on the surface of the nanospheres. Meanwhile, the thin gold layer can also serve as an ideal base on which chemical or biological agents can be functionalized. These molecules generate a repulsive force, preventing the particles from coming into contact and thus suppressing the destabilizing effect of the van der Waals interaction. In practical applications, this approach is often used in combination for the majority of ferrofluids, since this allows the synthesis of suspensions which are stable over years (
2.2.1. Magnetic (iron oxide nanoparticles)
Magnetic iron oxide nanoparticles are the most investigated material in biomedical techniques, due to its superior biocompatibility with respect to other magnetic materials, either in form of oxides or pure metals. Several types of iron oxides exist in nature and can be prepared in the laboratory. Nowadays, only maghemite (γ-Fe2O3) and magnetite (Fe3O4) are able to fulfill the necessary requirements for biomedical applications. These requirements include sufficiently high magnetic moments, chemical stability in physiological conditions and low toxicity, not to mention the easy and economical synthetic procedures available for the preparation of these materials
The degree of atomic order in the iron oxide lattice, or in other words its degree of crystallinity, as well as the dispersity of the nanoparticles in terms of size and shape are critical parameters that affect their performance in diagnostic and therapeutic techniques as a contrast agent in magnetic resonance imaging (MRI) and hyperthermia, respectively. These parameters are strongly correlated to the approach for their synthesis
2.2.2. Synthesis of iron oxide nanoparticles
The common existing methods to synthesize the iron oxide nanoparticles are physical, chemical and biological methods. Comparatively, chemical methods, especially wet chemical ones are much simpler and more efficient
Hydrothermal synthesis techniques are an alternative method for the preparation of highly crystalline iron oxide nanoparticles
Biological methods,since nanomaterials have comparable dimensions to biological aggregates, bio-relatedsynthesis methods have been explored for novel nanoparticle synthesis. In biologicalmethods, synthesis and assembly of crystalline inorganic materials can be regulatedby biological organisms under environmentally benign conditions and desired chemicalcompositions and phases can be achieved. For example, the nucleation of semiconducting nanoparticles can be initiated in the presence of viruses expressing material-specific peptides. Other examples are the use of porous protein crystals, manipulation of bacteria to produce oxide nanoparticles and selection of metal-specific polypeptides from combinatorial libraries
2.2.3. Classification of iron oxide nanoparticles
There are many categories of iron oxide nanoparticles based on their overall diameter (including iron oxide core and hydrated coating). Iron oxide nanoparticles can be distinctly classified into super-paramagnetic iron oxide nanoparticles (SPIO NPs) between 300 nm and 3.5
On the other hand, the magnetic materials are characterized by the presence of magnetic dipoles generated by the spinning of some of their electrons. Each of these polarized electrons can be aligned in a parallel or antiparallel fashion with respect to the neighboring ones in the crystal lattice, and this type of interaction is what gives rise to the macroscopic magnetic effect that we can measure. Based on the magnetic response, the magnetic materials can be classified into; diamagnetic, paramagnetic, ferromagnetic, ferrimagnetic, anti-ferromagnetic and super-paramagnetic
Diamagnetic materials are characterized by coupled or paired magnetic dipoles, so there is no permanent net magnetic moment per atom. That is to say that these materials have not any interactions or slightly repelled with the magnetic field. The magnetic susceptibility of these materials is negative and independent on temperature.
Paramagnetic materials characterized by randomly oriented (or uncoupled) magnetic dipoles, this can be aligned only in the presence of an external magnetic field along its direction. This type of material has neither coercivity nor remanence, which means that when the external magnetic field is switched off the internal magnetic dipoles randomize again. No extra energy is required to demagnetize the material and hence the initial zero net magnetic moment is spontaneously recovered.
Ferromagnetic materials characterized by individual magnetic dipoles in a crystal, those can align parallel one to the other, hence exhibiting an enhanced collective response even in the absence of an external magneticfield. This is what is known as
Ferrimagnetic and anti-ferromagnetic materials, in contrast to the ferromagnetic situation, neighboring magnetic dipoles can align antiparallel in the lattice, which means that they will cancel each other i.e. repulsion of magnetic dipoles. This type of magnetic exchange can lead to two different situations. The first is
Super-paramagnetic materials, bulky sized particles of magnetic materials such as (Fe), (Co) or (Ni), as well as some of their alloys (FePt & FeCo) have ferromagnetic properties due to their multi-domain structures of the particles. In contrast, at the nanometerscale of approximately 14 nm, the multi-domain combined together forming a single domain crystal, which is classified as super -paramagnetic
2.2.4. Characteristics of magnetic nanomaterials for in vivobio-applications
When nanoparticles are used for
220.127.116.11. Size distribution
Most intravenous administrated nanoparticles are recognized as ‘‘foreign’’ from the body system and are eliminated immediately through macrophages of the mononuclear phagocytosis system (MPS) depending on the size. The size of particles usually refers to the total diameter of the particles including the core and the coating layer. It is well known that, the smallest diameter of capillaries in the body is 4 µm. So, NPs smaller than 4µm are taken up through cells of the reticuloendothelial system (RES) mainly in the liver (60–90%) and spleen (3–10%). While small particles up to 150 nm will be phagocytosed through liver cells. There is a tendency for particles larger than 200 nm to be filtered by the venous sinuses of the spleen, as well as will be captured and withheld in the lungs. In general, the large particles are eliminated faster from the blood, and have short plasma half-life-period compared to the small particles (
18.104.22.168. Surface charge and protein adsorption
Particles with large sizes and/or aggregations of small particles such as magnetic nanoparticles (MNPs) may be trapped causing emboli within the capillary bed of the lungs. Therefore, it is important to know the surface charge and aggregation behavior of the particles in the blood circulation system
All bare nanoparticles are unsuitable for
The surface charge also plays an important role during endocytosis process. There should be a slower uptake for negatively charged particles due to the negative ‘‘rejection’’ effect of the negatively charged cell membrane. However, the endocytosis index
The adsorption of proteins at the particle surface is called “
The surface charge and protein adsorption capability are more related to the surfactants bond to the nanoparticles surface. There is another important role of surfactants on nanoparticles, when the NPs are injected into human body as contrast agents, these nanoparticles must locate the targeting area accurately and rapidly. Appropriate surfactant could achieve such objective. Some experiments
22.214.171.124. Cellular uptake
Cellular uptake of nanoparticles is another issue that should be taken into account, when considering their use in diagnostic and therapeutic applications. The cellular uptake of nanoparticles is strongly dependent on particle size as it was proven
The cellular uptake of nanoparticles occurs through a process known as endocytosis, which can be generally classified into three processes depending on nanoparticles size. Phagocytosis process which is the predominant mechanism for uptake of large particles, phagocytotic activity increases with size of particles, whereas smaller particles<150 nm can be up-taken by all types of cells through pinocytosis process (cell drinking).The third is non-specific endocytosis or receptor-mediated endocytosis process
When nanoparticles are introduced into the body, several aspects can compromise its stability. First of all, the physiological media have different ionic strength as compared with the ultrapure water mainly used in laboratories: increasing the ionic strength of aqueous solution will suppress the electric double layer around the charged particles, resulting in a partial or total aggregation of the system. A similar behavior could be observed by the particles once they enter specific body compartments, due to a variation in pH with respect to the media in which the nanoparticles are initially dispersed. In addition, when nanoparticles are injected in the blood circulation system, a nonspecific adsorption of plasma proteins onto nanoparticles surface
The metabolism process of the nanoparticles is another issue that should be taken into account. For example, iron oxide nanoparticles can be present in two different oxidation states: the ferrous Fe (II) form which will be oxidized by endogenous molecular oxygen, resulting in the conversion of ferrous iron to ferric Fe (III). Ferric iron is the preferred physiological oxidation state of iron; Fe (III) is highly reactive and can induce catalytic activity that may result in severe oxidative cell damage. As a result, iron carrier proteins and chelates are used to allow for safe transfer of iron from cell to cell within the body, and for safe intra-cellular storage of excess iron.The natural eventual fate of Fe3O4 nanoparticles above approximately 200 nm in diameter is to reside in macrophage-rich tissue, such as the liver and spleen (peak concentration at 2 hours after contrast intake).While particles below 10 nm are removed rapidly through extravasations and renal clearance
Biocompatibility is one of the most important considerations in the development of biomedical applications of nanomaterials. Most of the magnetic nanowires are compatible with living cells. They can be functionalized with biologically active molecules, and they do not disrupt normal cell functions, such as cell proliferation and adhesion, and gene expression (
The non-cytotoxic, non-immunogenic and biocompatible properties of nanoparticles are important issues for the potential application in nanoimmunology, nanomedicines and nanobiotechnology. When discussing the toxicity of nanoparticles, generalization becomes difficult because their toxicity depends on numerous factors including the dose, chemical composition, method of administration, size, biodegradability, solubility, pharmacokinetics, biodistribution, surface chemistry, design, shape and structure. In general, size, surface area, shape, composition and coating of nanoparticles are the most important characteristics regarding cytotoxicity
To minimize the risks posed by nanoparticles, there are two basic avenues. One is to develop new highly biocompatible nonmaterials with low toxicity such as silica nanoparticles. Another one is the surface modification of nanoparticles with biocompatible chemicals such as PEG, dextrin and chitosan. Thus many great efforts are being made to develop nanoparticles satisfactory for biomedical applications
126.96.36.199. Easy detection
As almost all biological entities are non-magnetic, magnetic nanoparticles in biological systems can be easily detected and traced. One typical example is the enhancement of the signal from magnetic resonance imaging (MRI) using magnetic nanoparticles. In this technique, a subject is placed in a large, external magnetic field and then exposed to a pulse of radio waves. Changes to the spin of the protons in water molecules are measured after the pulse is turned off. Tiny differences in the way that protons in different tissues behave can then be used to build up a 3D image of the subject (
188.8.131.52. Magnetic manipulation
Magnetic nanoparticles will rotate under an external uniform magnetic field, and will make translational movements under an external magnetic field gradient. Therefore, magnetic nanoparticles, or magnetically tagged molecules, can be manipulated by applying an external magnetic field. This is important for transporting magnetically tagged drug molecules to diseased sites. The magnetic manipulation of magnetic nanowires and nanotubes is important for applying forces to biological entities, and for nanowires or nanotubes to get into biological entities.
184.108.40.206. Energy transfer
Magnetic nanoparticles can resonantly respond to a time-varying magnetic field, transferring energy from the exciting magnetic field to the nanoparticles and the tagged biological entities. This property has been used in hyperthermia treatment of cancer tumors (
2.2.5. Biomedical applications of iron oxide NPs
Nanotechnology, dealing with nanoscale objects, has been developed at three major levels: nanomaterials, nanodevices and nanosystems. At present, the nanomaterials level is the most advanced of the three. Nanomaterials are of great importance both in scientific investigations and commercial applications due to their size-dependent physical and chemical properties. Nanomaterials with various shapes have been developed successfully. Common morphologies are quantum dots, nanoparticles/nanocrystals, nanowires, nanorods, nanotubes, etc. It is desirable to have a full range within the nanomaterial family because many applications demand particular nanomaterials with special structures.
Magnetic nanoparticles, being a sub-family of nanomaterials, exhibit unique magnetic properties in addition to other specific characteristics. Their remarkable new phenomena include super-paramagnetism, high saturation field, high field irreversibility, extra anisotropy, and temperature-depended hysteresis, etc. Research investigation has revealed that the finite size and surface effects of magnetic nanoparticles determine their magnetic behavior. For instance, a single magnetic domain forms when the size of a ferromagnetic nanoparticle is less than 15 nm. In other words, an ultrafine ferromagnetic nanoparticle displays a state of uniform magnetization under any field. Thus, at temperatures above the blocking temperature, these nanoparticles show identical magnetization behavior to atomic paramagnets (super-paramagnetism) with an extremely large magnetic moment and large susceptibilities.
Magnetic nanoparticles have found many successful industrial applications. Recently, tremendous research efforts have been stimulated on the usage of magnetic nanoparticles in the field of biomedical and biological applications.
Understanding of biological processes and hence developing biomedical means have been continuously pursued. These aims are one of strong driving forces behind the development of nanotechnology. The interests on magnetic nanoparticles for bio-applications come from their comparable dimensions to biological entities coupled with their unique magnetic behaviors. Though common living organisms are composed of cells of about 10 μm size, the cell components are much smaller and generally in the nanosize dimension. Examples are viruses (20–450 nm), proteins (5–50 nm) and genes (2 nm wide and 10–100 nm long). Synthetic magnetic nanoparticles have controllable dimensions and just a few nanometer-diameter nanoparticles can be synthesized by carefully designing experimental procedures and controlling experimental conditions. With such a nanoscale dimension, it would be possible for magnetic nanoparticles to get close to a biological entity of interest. Moreover, the interaction between magnetic nanoparticles and biological entities can be adjusted by coating nanoparticles with biological molecules, called bio-functionalization. This offers a controllable means of ‘tagging’ or addressing the binding at nanoscale. The comparable dimensions and magnetic properties of magnetic nanoparticles have prompted the idea of using them as very small probes to spy on the biological processes at the cellular scale without introducing too much interference. Actually, optical and magnetic effects have been treated as the most suitable approaches for biological applications owing to their non-invasive behavior.
In view of the magnetic properties of magnetic nanoparticles, they can be manipulated by an external magnetic field gradient, which is described by Coulomb’s law. Magnetic nanoparticles are able to transport into human tissues due to the intrinsic penetrability of magnetic fields into human bodies. This ‘action at a distance’ opens up many potential bio-applications including transportation of magnetically tagged biological entities, targeted drug delivery, etc. Another important property of magnetic nanoparticles is their resonant response related to a time-varying magnetic field
The magnetic properties of magnetic nanoparticles are determined by their elemental compositions, crystallinity, shapes and dimensions. Various magnetic nanoparticles have been developed. Therefore, the selection of proper magnetic nanoparticles with the desired properties is the first but crucial step for certain bio-applications. For example, ferromagnetic nanoparticles (e.g. Fe nanoparticles) have a large magnetic moment and they can be the best material candidate in magnetic biosensors because they not only produce a better signal but respond to an applied magnetic field readily. On the other hand, iron oxide nanoparticles with super-paramagnetic behavior do an excellent job when used to enhance the signals in magnetic resonance imaging examinations. With the help of iron oxide nanoparticles a sharpened image with detailed information can be achieved because of the change of behavior of nearby bio-molecules by introduced nanoparticles
It is no doubt that interdisciplinary research collaboration is badly needed for clinical and biological applications of magnetic nanoparticles
3. Hyperthermia treatment
Another major use of magnetic nanoparticles in therapeutic treatment is hyperthermia treatment for cancers. Gilchrist
Magnetic nanoparticles can be divided into two major categories: multi-domain and single-domain nanoparticles, which possess different heating effects. Multi-domain nanoparticles usually have larger dimensions and contain several sub-domains with definite magnetization direction for each. When they are exposed to a magnetic field, a phenomenon called ‘domain wall displacements’ occurs. This is featured by growth of the domain with magnetization direction along the magnetic field axis and shrinkage of the other. Figure 2 above, depicts this irreversible phenomenon. It can be seen that the magnetization curves for increasing and decreasing magnetic field do not coincide, and the area within the hysteresis loop represents the heating energy, named ‘hysteresis loss’, due to the AC magnetic field. For single-domain nanoparticles, since there is no domain wall, no hysteresis loss occurs leading to no heating. When exposed to an external AC magnetic field, rotation of magnetic moments from super-paramagnetic nanoparticles is assisted by the supplied energy which overcomes the energy barrier. Then these nanoparticles undergo N´eel relaxation in which their moments relax to their equilibrium orientation. Simultaneously, heat is generated during this relaxation by thermal dissipation. The N´eel relaxation time tN is related to the temperature, and can be described as:
Where t0 ≈ 10−9 s, T is the temperature and k is the Boltzmann constant.For both multi- and single-domain nanoparticles, rotational Brownian motion in a carrier also generates heat. This rotation is caused by the torque exerted on the magnetic moment by the AC magnetic field. The Brown relaxation time tB is described as:
The heating capacity of magnetic nanoparticles is expressed by specific absorption rate SAR, also called specific power loss (SPL), both of them have the same physical meaning, which determines the heating ability of magnetic nanoparticles in the presence of magnetic field, and can be defined as the amount of heat generated per unit gram per unit time. SAR values are usually expressed inwatts per gram of magnetic material (W/g), also can be expressed in volumetric units(W/m3).The heat generated per unit volume can be obtained by multiplyingthe SAR value by the density of the nanoparticles. It has been well documentedthat the orientation and magnetized domains of magnetic nanoparticles are dependent ontheir intrinsic features (elemental composition, crystallinity, magneto anisotropy, shape,dimension, etc.) and micro-structural features (impurities, grain boundaries, vacancies,etc).In magnetic hyperthermia treatment, after heat conducts into the area with diseased tissues, the surrounding temperature can be maintained above the therapeutic threshold of 42 ◦C for about half an hour to destroy the cancer. It is of great importance for hyperthermia to minimize the heat effect on healthy cells. Assisted by magnetic nanoparticles, it is possible to heat the specific area while unacceptable coincidental heating of healthy tissue is avoided. Although the hyperthermia treatment for cancer has been demonstrated with therapeutic efficacy in animal models, however, there have been no reports of successful hyperthermia treatment for human patients. The major reasons are the necessities of an adequate amount of magnetic nanoparticles and sufficiently high magnetic field which are not safe for human treatments. To date, laboratory research efforts on hyperthermia treatment for animals have all used magnetic field conditions which are not clinically acceptable. In most instances, hyperthermia treatments with a reduced amount of magnetic nanoparticles and reduced field strength or frequency cannot be effective due to the reduction of heat generated. Simulations suggest a sufficient level with heat deposition rate of 100mWcm−3 to destroy cancer cells effectively in most circumstances. The practical frequency and strength of the external AC magnetic field are 0.05–1.2MHz and 0–15 kAm−1, respectively. On the other hand, sufficient magnetic materials are needed to enrich around the cancer tissues to generate enough heat for hyperthermia treatment. Direct injection of ferrofluid into the tumor tissues is able to introduce a large amount of magnetic materials for heat generation. Antibody targeting and intravascular administration offer better preference heating, but the problem here is the small quantity. It is estimated that about 5–10 mg of magnetic material concentrated in each cm3 of tumor tissues is able to generate enough heat for tumor cell destruction in human bodies. Magnetite (Fe3O4) and maghemite (
The history of using magnetic particles for selective heating of the tumors started in 1957 when Gilchrist et al used particles of a few mm in size for inductive heating of lymph nodes in dogs (
Fumiko et al 2004 developed magnetite cationic liposomes (MCLs) and applied them to local hyperthermia as a mediator. MCLs have a positive charge and generate heat under an alternating magnetic field (AMF) by hysteresis loss. In this study, the effect of hyperthermia using MCLs was examined in an in vivo study of hamster osteosarcoma. In this study, three-week-old Syrian female hamsters were purchased from Japan SLC, Inc., Shizuoka, Japan, and used for the animal study. After that MCLs were injected into the osteosarcoma and then subjected to an AMF. The results revealed that, the tumor was heated at over 42°C, but other normal tissues were not heated as much. Complete regression was observed in 100% of the treated group hamsters, whereas no regression was observed in the control group hamsters. At day 12, the average tumor volume of the treated hamsters was about 1/1000 of that of the control hamsters. In the treated hamsters, no regrowth of osteosarcomas was observed over a period of 3 months after the complete regression. These results suggest that this treatment is effective for osteosarcoma.
One of recent and novel study was applied by El Sherbini et al (2011). The aim of this experimental study is to evaluate the effect of magnetic resonance on magnetic nanoparticles, this
Preparation of tumors bearing mice and iron oxide magnetic nanoparticles followed the method described by Elsherbini et al (2011). The prepared SPIO nanoparticles were suspended in glycerin medium to increase the stability especially
The results of heat deposition rate HDR inside the tumor revealed that, the mean values of HDR were [0.157 for (200µg), 0.259 for (400µg), and 0.367 for (600µg), 0.478 for (800µg) and 0.604 for (103µg)] as shown in figure (4). These values varied considerably between the different concentrations of SPIO nanoparticles with highly significant
Plasmonic photo-thermal therapy (PPTT).Gold nanoshells belong to a prospective class of optical adjustable nanoparticles with a dielectric silica core encased in a thin metallic gold shell (Hirsch, et al 2006). The absorption cross-section of a solid nanoshell is high enough to provide a competitive nanoparticle technology with application of indocyanine green dye, a typical photothermal sensitizer used in laser cancer therapy (Gupta, et al 2007).
On the other hand, there are several
In a study by El- Sayed and co-workers conjugated gold nanoparticles of approximately 40 nm to anti-epithelial growth factors receptors (EGFR) antibodies and targeted to types of human head and neck cancer cells, the nanoparticles induce cancer cell damage at 19 W/cm2 after the irradiation with argon Ar+ laser at 514 nm for 4 min, while healthy cells do not show the loss of cell viability under the same treatment
Huang et alalso described the photo-thermal destruction of cancer cells using bio-functionalized gold nanorods. The nanorods were conjugated to anti- EGFR (specific antibody to the malignant cell types used), and then incubated with a non-malignant epithelial cell line (HaCat), as well as two malignant oral epithelial cell lines (HOC313 clone8 and HSC3). Following laser irradiation, the results revealed that the malignant cells were destroyed at about half the laser fluence needed to kill the nonmalignant cells. The efficient destruction of the malignant cells was evidently due to the preferential attachment of the anti-EGFR-gold nanorod conjugates to the over-expressed EGFR on the surface of the malignant cell
In 2006, El-Sayed and co-workers conjugated gold nanorods to anti-EGFR antibodies specifically bind to the head and neck cancer cells, these labeled cells subjected to laser irradiation (Ti: Sapphire laser, CW at 800 nm) which was maximally overlapped with the surface plasmonic resonance absorption band of the nanorods. Under laser exposure for 4 min, it was found that the cancer cells required half the laser energy (10 W/cm2) to be photo- thermally damaged as compared to the normal cells (20 W/cm2)
In 2007, Huff and co-workers conjugated folate ligands with oligo-ethylene-glycol onto gold nanorods by
Attempts using gold nanocages for PPPT have also been made recently. In the
Paul and Tuanreported the application of liposome-encapsulated gold nanoshells for in vitro photo-induced hyperthermia in human mammary carcinoma cells. In addition to evaluating their effects in vitro, the authors compared the application liposome-encapsulated gold nanoshells and free-standing gold nanoshells for NanoPhotoTherapy (NPT). NPT-induced hyperthermia was performed using a 785-nm near-infrared light from a diode laser and the in vitro effects were evaluated using nucleic acid molecular probes by fluorescence microscopy. Additionally, they monitored the effectiveness of NPT by detecting apoptosis via capase-9 activity.The experiments clearly showed that liposomal deliveryenhanced the intracellular bioavailability of gold nanoshellsand thus is able to induce a higher degree of cell death moreeffectively than free-standing gold nanoshells.
Single-walled carbon nanotubes (SWNTs) have a high optical absorbance in the near-infrared (NIR) region. In this special optical window, biological systems are known to be highly transparent. The optical properties of SWNTs provide an opportunity for selective photo thermal therapy for cancer treatment. Specifically, SWNTs with a uniform size about (0.81 nm) and a narrow absorption peak at 980 nm are ideal candidates for such a novel approach. In a study by Feifan et al, SWNTs are conjugated to folate, which can bind specifically to the surface of the folate receptor tumor markers. Folate- SWNT (FA-SWNT) targeted tumor cells were irradiated by a 980 nm laser. Results in
Kim et al achieved close to 90% cancer cell destruction in vitro using FeNi@Aumagnetic-vortex microdiscs (MDs), on the application of only a few tens of hertz AMF for just 10min. This confirms that operation of MFH at lower frequencies is possible and for effective heat generation can be achieved using core–shell type of structures. Likewise, in yet another demonstration, a gold coating of approximately 0.4 to 0.5 nm thickness around SPIONs resulted in a four- to five-fold increase in the amount of heat released (the highest value of 976W/g in ethanol at 430 Hz frequency) in comparison with SPIONs on application of low frequency oscillating magnetic fields (44–430 Hz). This study was done by Mohamed et al 2010. In addition, the SPIONs@Au were found to be not particularly cytotoxic to mammalian cells. (MCF-7 breast carcinoma cells and H9c2 cardiomyoblasts) in
In this context, a study was done by Elsherbini and co-workers, 2011. The group evaluated two different approaches in the nanotechnology era for inducing hyperthermia in subcutaneous Ehrlich carcinoma cells. The first called Optical Resonance Hyperthermia (ORH) technique in presence of gold nanospheres and green diode laser, as shown in fig (9). While the second technique calledMagneto-Optical Resonance Hyperthermia (MORH), in presence of gold-iron oxide core shell nanoparticles with green, near infra-red diode laser, and magnetic field,as shown in fig (10). This approach was performed under magnetic resonance imaging guidance. The results revealed that, all mice treated by the first technique, the tumors were still as the same as before the treatments, as well as the rate of tumors growth were very slow if compared with the control mice. In contrast more than 50% of the mice treated with the second technique revealed a complete disappearance of the tumor, as shown in figure (11). So the study have demonstrated that a pair of synthetic nanospheres can work together more effectively for inducing hyperthermia than individual nanospheres, whereby more than.So, this simple, non-invasive method shows great promise as a treatment technique for clinical setting.
There are two main advantages of the plasmonic photothermal therapy technique. Firstly, there is the benefit of photostability compared with the photosensitizer dyes used in photodynamic therapy, which suffer from photobleaching as well as diffusion under laser irradiation. Secondly, there is the advantage of absorption and scattering cross-sections of gold nanoparticles, which are significantly superior to the absorbing dyes conventionally used in biological systems. Mie theory estimates that the optical cross-sections of gold nanospheres are typically four to five orders of magnitude higher than those of conventional dyes.
In spite of much progress having been made using the plasmonic photothermal therapy technique for cancer treatment in a laboratory setting, there are still many factors which must be taken into account before this method may be taken to a clinical setting, and they need to be studied further. First of all, the distribution of the elevated temperature under plasmonic photothermal therapy treatment is related to absorption of light by nanospheres acting as point wise local heat sources and by thermal diffusion over surrounding tissues. At the practical level, plasmonic photothermal therapy needs to provide an appropriate temperature increment,
Although interstitial hyperthermia following direct injection of nanoparticles has been proven successful in many animal models, nevertheless only one of these approaches has been successfully translated from research to clinical stage for prostate cancer treatment either by iron oxide against RF,this clinical studies were performed by Johannsen 2005. The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0–18 kAm_1). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anesthesia. In the first patient treated, maximum and minimum intraprostatic temperatures measured at field strength of 4.0–5.0 kAm_1 were 48.50C and 40.00C during the 1st treatment and 42.50C and 39.40C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors’ knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.
Akihiko et al have developed a novel hyperthermic treatment modality using magnetic materials for metastatic bone tumors. The purpose of this study is to show the results of novel hyperthermia for metastatic bone tumors. This novel hyperthermic treatment modality was used for 15 patients with 16 metastatic bone lesions. In seven lesions, after curettage of the metastatic lesion followed by reinforcement with a metal intra-medullary nail or plate, calcium phosphate cement (CPC) containing powdery Fe3O4 was implanted into the cavity. In one lesion, prosthetic reconstruction was then performed after an intralesional tumor excision. For the remaining eight lesions, metal intra-medullary nails were inserted into the affected bone. Hyperthermic therapy was started at 1 week postoperatively. To comparatively evaluate the radiographic results of patients who underwent hyperthermia (HT group), the authers also assessed eight patients who received a palliative operation without either radiotherapy or hyperthermia (Op group), and 22 patients who received operation in combination with postoperative radiotherapy (Op + RT group). In HT group, all patients had an acceptable limb function with pain relief without any complications. On radiographs, 87, 38, and 91% were, respectively, considered to demonstrate an effective treatment outcome in HT group, Op group, and Op + RT group. The patients in HT group showed a statistically better radiographic outcome than the patients in Op group (P = 0.0042). But when compared between HT group and Op + RT group, there were no significant difference (P = 0.412). This first series of clinical hyperthermia using magnetic materials achieved good local control of metastatic bone lesion.
Study by Manfred et al 2007, or by using laser against gold nanoparticles, for instance Yusheng et al 2009 used core shells (silica as a core with a diameter 110nm and an outer gold shell with thickness 15 nm) to mediate laser surgery stimulation for prostate cancer treatment. The goal of this paper is to present an integrated computer model using a so-called nested-block optimization algorithm to simulate laser surgery and provides transient temperature field predictions. In particular, this algorithm aims to capture changes in optical and thermal properties due to nanoshell inclusion and tissue property variation during laser surgery. Numerical results show that this model is able to characterize variation of tissue properties for laser surgical procedures and predict transient temperature field comparable to that measured by in vivo magnetic resonance temperature imaging (MRTI) techniques. Note that the computational approach presented in the study is quite general and can be applied to other types of nanoparticle inclusions.
In conclusion, this is abrief review on different approaches for inducing hyperthermia cancer treatment relevant to nanomedicine