Understanding MNPs Behaviour in Response to AMF in Biological Milieus and the Effects at the Cellular Level: Implications for a Rational Design That Drives Magnetic Hyperthermia Therapy toward Clinical Implementation

Abstract

Hyperthermia has emerged as a promising alternative to conventional cancer therapies and in fact, traditional hyperthermia is now commonly used in combination with chemotherapy or surgery during cancer treatment. Nevertheless, non-specific application of hyperthermia generates various undesirable side-effects, such that nano-magnetic hyperthermia has arisen a possible solution to this problem. This technique to induce hyperthermia is based on the intrinsic capacity of magnetic nanoparticles to accumulate in a given target area and to respond to alternating magnetic fields (AMFs) by releasing heat, based on different principles of physics. Unfortunately, the clinical implementation of nano-magnetic hyperthermia has not been fluid and few clinical trials have been carried out. In this review, we want to demonstrate the need for more systematic and basic research in this area, as many of the sub-cellular and molecular mechanisms associated with this approach remain unclear. As such, we shall consider here the biological effects that occur and why this theoretically well-designed nano-system fails in physiological conditions. Moreover, we will offer some guidelines that may help establish successful strategies through the rational design of magnetic nanoparticles for magnetic hyperthermia.

Emerging Application of Magnetic Nanoparticles for Diagnosis and Treatment of Cancer

“…This approach offers an alternative for certain cancers that may be difficult to surgically remove and for those that reside proximally to vital organs. Since magnetic hyperthermia resolves the issue of nonselective ionizing radiation associated with conventional radiotherapy, treatment options may broaden beyond certain tumours [ 93 ]. Magnetite and maghemite are the most utilized nanoparticle materials for magnetic hyperthermia [ 30 ].…”

“…Increased temperatures also enhance cell sensitivity to alternative treatments such as chemotherapy and radiation [ 96 ]. Moreover, the increase in cancer cell sensitivity can be attributed to the improved anti-tumour immune response caused by hyperthermia due to its ability to enhance the presentation of tumour antigens, trafficking of leukocytes throughout the endothelium, and NK cell and dendritic cell activation [ 93 ]. The degree of sensitivity is dependent on the time taken between heating and chemotherapy, drug nature and concentration, tumour type, and tumour temperature [ 97 ].…”

“…The reduction of tumour cell viability through amplified cathepsin D activity within the cytoplasm is another consequence of increased lysosomal permeability. Furthermore, the rotation of SPIONs induced by dynamic magnetic fields may disrupt lipid membrane stability, thereby influencing lysosomal permeability and resulting in the activation of apoptosis [ 93 ].…”

“…Therefore, it is essential that thermal biological studies are undertaken to gain a further understanding. The thermotolerance and the effect of hyperthermia on cells on a molecular level, including the sensitives of various cancer types to temperature, should also be assessed [ 93 ].…”

Nanoparticles for Magnetic Heating: When Two (or More) Is Better Than One

“…In a different strategy, magnetic NPs can be incorporated into a biocompatible matrix together with drug molecules (bound to the NPs or loaded separately) and magnetic heating can be used to induce the controlled degradation of the matrix and the targeted release of the drug, maximizing its effect and monitoring the treatment [ 6 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Comprehensive review articles can be found in the literature, well illustrating the latest advances and future prospects in biomedical applications of magnetic heating through NPs [ 24 , 25 , 26 , 27 , 28 , 29 ].…”