Novel Approach for Magnetic Nanoparticle-based Hyperthermia for Metastatic Cancer Treatment

Abstract

Hyperthermia has been defined as the process of increasing the temperature of the body or a particular region of it beyond the threshold level set at a particular moment by the thermoregulatory system of an organism [1]. The stage of the cancer, the locations of malignancies and their depths inside the body, play a role when choosing the appropriate method of clinical hyperthermia application out of the existing three standard options: whole-body, regional, or local hyperthermia. While whole-body heat application is used to treat deep seated and disseminated malignancies, local or regional treatments deliver heat to localized or advanced cancer, respectively [2]. During the last decades, hyperthermia has been only used in combination with radiotherapy or chemotherapy mainly due to operational constraints and the incidence of harmful secondary effects that were found to affect the surrounding healthy tissues [3,4]. Some thermal damage, such as the appearance of burns on external tissue, is a common side effect of treatment. This can be avoided by maximizing toxic effects on the tumor area and confining the heating to the volume of the tumor mass [1]. In addition to thermal damage, transient adverse effects such as vomiting, diarrhea, and nausea may appear. On rare and extreme occasions cardiac, vasculature and cerebral disorders may arise [5,6]. Since these occurrences are highly uncommon, and the ability to control, monitor, and understand hyperthermia and its effects has increased over recent years, its side effects are generally considered to be not serious, especially in comparison to other cancer treatments [5].Several studies testing the clinical benefits of hyperthermia have been performed, providing evidence that hyperthermia is less efficacious when applied as a single therapy, with limiting factors such as the reproducibility of heat deposition into the tumor mass, the formation of hotspots [4,7], and the challenging measurement of the temperature within the tumor and its vicinity.Nevertheless, hyperthermia has been demonstrated in trials to prolong life and decrease disease re-appraisal as an adjuvant therapy, damaging cancer cells and causing radiation and chemosensitization, with some tumors being more responsive than

A Validated Methodological Approach to Prove the Safety of Clinical Electromagnetic Induction Systems in Magnetic Hyperthermia

“…Hyperthermia Treatment Planning (HTP) has increasingly made its way into clinical use in recent years. Current alternative treatments in MNP hyperthermia primarily focus on localized therapy, where tumors are identified, located, and then, directly injected with MNPs for targeted irradiation, as exemplified in systems, like the one by MagForce AG [31], that involve HTP [32]. The MNH system presented in this study introduces a method of regional irradiation, treating the patient's entire torso, thus eliminating the need for precise tumor detection and localization.…”

Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model

“…Hyperthermia, the process of raising the temperature of tumor-loaded tissue to 40-43°C results in the denaturation of proteins and structural damage within cancer cells (4). During the last decades, hyperthermia based-cancer treatment has been applied safely mainly as an adjuvant therapy (5).…”

“…Sarah Nanotechnology comprises of: (i) Sarah Nanoparticles (SaNPs), containing encapsulated iron oxide (IO) nanoparticles, that attach to cancer cells, and an (ii) electromagnetic induction system (EIS) that generates an alternating current magnetic field (AMF) that is converted to heat by the SaNPs due to their magnetic properties. The applied AMF heats the SaNPs to a predefined and controllable temperature, thereby offering an innovative approach to treat cancer by inducing non-ablative thermic damage (5).…”

“…Following delivery and attachment of the SaNPs to the malignant cells, the patient undergoes regional 290 ± 10% kHz AMF application with the EIS generating a magnetic field at a range of 8-33 kA/m, the SaNPs subsequently convert the applied AMF to latent heat and retain it, and the PCM core controls and stabilizes the SaNP temperature to 50 ± 3°C, thereby using this heat to cause hyperthermic cancer cell death without harming healthy cells under a magnetic field. The main innovation of the SaNP lies in its inherent ability to control its temperature without inducing thermal ablation which occurs at temperatures above 60°C (5). Previous studies examining the PCM's functionality and the temperature control property have demonstrated that SaNPs exposed to AMF irradiation with an amplitude of 33.4 kA/m at 300 kHz for 30 minutes stabilize at a temperature plateau between 48-52°C, in agreement with the melting phase transition temperature range of the PCM component (8).…”