Biologically Targeted Magnetic Hyperthermia: Potential and Limitations

Abstract

Hyperthermia, the mild elevation of temperature to 40–43°C, can induce cancer cell death and enhance the effects of radiotherapy and chemotherapy. However, achievement of its full potential as a clinically relevant treatment modality has been restricted by its inability to effectively and preferentially heat malignant cells. The limited spatial resolution may be circumvented by the intravenous administration of cancer-targeting magnetic nanoparticles that accumulate in the tumor, followed by the application of an alternating magnetic field to raise the temperature of the nanoparticles located in the tumor tissue. This targeted approach enables preferential heating of malignant cancer cells whilst sparing the surrounding normal tissue, potentially improving the effectiveness and safety of hyperthermia. Despite promising results in preclinical studies, there are numerous challenges that must be addressed before this technique can progress to the clinic. This review discusses these challenges and highlights the current understanding of targeted magnetic hyperthermia.

PEGlatyon-SPION surface functionalization with folic acid for magnetic hyperthermia applications

“…This therapeutic platform is based on controlled heating of tumor tissue through the accumulation of SPION within cancer cells followed by exposure to an external alternating magnetic field (AMF). The SPION act as nano-heaters by increasing the local temperature in the range of 41-46°C [11,12], which triggers cell death mechanisms (apoptosis or/and necrosis) while altering the functionality of the protein causing high sensitivity of the cancer cells to traditional treatments (e.g. radiotherapy and chemotherapy) [13].…”

Use of magnetic fields and nanoparticles to trigger drug release and improve tumor targeting

“…Two approaches are most common: (a) the use of magnetic particles to improve the accumulation of drugs in a desired region via magnetic targeting (Alexiou et al, 2000;Shapiro et al, 2015) and (b) the use of magnetic fields to heat magnetic particles to directly induce hyperthermia in or ablation of diseased tissues (Hedayatnasab, Abnisa, & Daud, 2017) and/or to trigger the release of drugs from thermally sensitive carriers (Moros et al, 2019;Yoo, Jeong, Noh, Lee, & Cheon, 2013; Figure 1). As there are already a number of very comprehensive reviews on hyperthermia and thermal tissue ablation (Chang et al, 2018;Dewhirst, Lee, & Ashcraft, 2016;Périgo et al, 2015), these topics will not be discussed extensively here. Rather, we focus on approaches that have been developed for magnetic targeting of drug-loaded magnetic nanocarriers as well as magnetically induced drug release.…”

Heat-triggered remote control of CRISPR-dCas9 for tunable transcriptional modulation

“…Here, we integrate heat as a remote trigger with the rapidly expanding CRISPR toolbox to confer tunable remote control of orthogonal transcriptional commands. In contrast to chemical or optical cues, pulses of heat can be delivered noninvasively with millimeter precision and at depth to anatomical sites by various approaches, such as infrared light 11 , high-intensity focused ultrasound 12 , or magnetic particles in alternating magnetic fields 13 . Recent control methods based on heat-induction to modulate gene expression [14][15][16][17] include genetically encoded RNA thermometers 14 and temperature-sensitive transcriptional regulators 16 .…”

“…After demonstrating transcriptional modulation in vitro, we next set out to implement this system for remote thermal control of gene expression in vivo. Spatially controlled delivery of heat is routinely employed in thermal medicine to improve treatment efficacy of drugs and can be accomplished by various modalities such as plasmonic photothermal heating [11][12][13] . To implement this system in vivo, we subcutaneously implanted tissue phantoms in the rear flank of nude mice (Figure 2d).…”