Cancer Treatment: Multifunctional Magnetic Nanoparticles for Molecular Imaging and Hyperthermia
Hyperthermia involves heating up of local environment of a tumor resulting in cell damage and death. Tumor cells are more sensitive to high temperature than normal cells, hence hyperthermia doesn’t affect normal cells. It is an adjuvant cancer therapy used to enhance the efficacy of traditional therapies such as radiotherapy and chemotherapy, surgery, gene therapy, and immunotherapy for cancer.
Hyperthermia treatment can be classified into different types on the basis of temperature raised:-
- Thermal ablation, in which a tumor is heated to high temperatures greater than 46°C (up to 56°C) causing tissue necrosis, and coagulation.
- Moderate hyperthermia, which uses temperature between 41°C to 46°C to heat tumor cells resulting in denaturation and aggregation of proteins, protein folding, crosslinking of DNA leading to apoptosis and heat shock protein (HSP) expression. It also leads to perfusion and oxygenation and change in pH of tumor microenvironment.
- Diathermia uses temperatures less than 41°C for the treatment of rheumatic diseases.
The effectiveness of hyperthermia treatment depends on the temperature generated at the targeted site(s), time of exposure and characteristics of tumor cells.
On the basis of location of disease or tumor, hyperthermia can be classified as:-
- Local hyperthermia, in which heat is applied to a small area, such as a tumor. Radiowaves, microwaves, ultrasound waves can be used to heat the area. The heat may be applied either internally or externally.
- Regional hyperthermia, in which heat is applied to large areas of tissue or organ. Sometimes some of the patient’s blood is removed, heated, and then pumped (perfused) back into the tissue or organ. Anticancer drugs are also administered during this treatment.
- Whole-body hyperthermia is used to treat metastatic cancer that has spread throughout the body.
The clinical applications of hyperthermia faces challenge such as restricting heat to tumor cells only, without damaging healthy tissues and reduced effectiveness of heating due to the expression of heat shock proteins resulting in heat tolerance in cells. Blood flow at tumor sites is also irregular and poses several challenges, but if significant localized heating is achieved hyperthermia can be effective. Also there is limited penetration of heat into body tissues by microwave, laser, and ultrasound waves.
Magnetic Hyperthermia and Magnetic Nanoparticles (MNP)
Localized heating can be achieved by Magnetic hyperthermia. It involves delivering magnetic nanoparticles (MNPs) at the tumor site and applying an alternating magnetic field (AMF).
MNPs dissipate heat in an applied AMF due to relaxation of rotating magnetic moments. Tumors are typically heated to 41°C to 47°C, as tumor cells possess higher heat-sensitivity over normal cells, this results in damage to tumor cells only.
In a study by Johannsen et al. magnetic nanoparticle mediated hyperthermia combined with less dose of radiation demonstrated equivalent therapeutic efficacy compared to larger dose of radiation alone in a rat prostate cancer model.
Magnetic nanomaterials advantages:
A number of magnetic nanomaterials, including iron oxide (Fe3O4 and γ-Fe2O3) based nanomaterials and oxides of metallic NPs such as Mn, Co, Ni, Zn, Gd have been investigated for their potential for hyperthermia. Iron oxide nanoparticles (Fe3O4 and γ-Fe2O3) are stabilized by a variety of ligands such as dextran, PEG, polyvinyl alcohol, to increase their circulation time in the body and to prevent clearance by MPS. Another class of magnetic material is based on ferrites such as cobalt ferrites (CoFe2O4), manganese ferrite (MnFe2O4), nickel ferrite (NiFe2O4) etc.
- Iron oxide-based MNPs are non toxic and have excellent biocompatibility, and they can be metabolized to form blood haemoglobin, and hence maintain homeostasis of iron inside cells.
- MNPs can be targeted to specific tumor cells.
- As a result, concentration of MNPs would be more at tumor sites thereby increasing the effectiveness of hyperthermia.
Magnetic Nanoparticles (MNPs) offer an opportunity to create multifunctionality with potential to diagnose and treat a number of diseases. Controlled drug release is very important in drug delivery for treatment of tumors and other diseases. Drug release from MNPs can be triggered by external stimuli, MNPs along with therapeutic molecules are encapsulated in a pH or heat sensitive polymers. Upon application of AMF (in case of heat sensitive polymers, for pH sensitive polymers pH of tumor microenvironment is stimuli), MNPs will generate heat leading to formation of pores in polymers, thus releasing therapeutic molecules.
Magnetic nanoparticles (Fe3O4) can also be used as contrast enhancing agent in Magnetic Resonance Imaging (MRI) for real time monitoring of treatment progression and in cancer diagnosis and prognosis.
Challa S.S.R. Kumar, Faruq Mohammad, Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery, Advanced Drug Delivery Reviews, Volume 63, Issue 9, 14 August 2011, Pages 789-808, ISSN 0169-409X, 10.1016/j.addr.2011.03.008.
Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi, Medical application of functionalized magnetic nanoparticles, Journal of Bioscience and Bioengineering, Volume 100, Issue 1, July 2005, Pages 1-11, ISSN 1389-1723, 10.1263/jbb.100.1.