Precision in Thermal Therapy: Clinical Requirements and Solutions from Nanotechnology

Abstract

The heating of diseased tissue as a therapeutic measure has gained increased clinical attention, mostly due to its target-specificity that minimizes side effects. However, to ensure a successful therapy, heating has to be homogeneous and highly localized, as well as, within a certain temperature range. Therefore, precise control over thermal treatments is a clinical prerequisite to minimize treatment and safety margins. Although this requirement is mentioned frequently, past research has focused predominantly on improving thermometry resolution and heating efficiency through tedious material optimization. Here, current clinical applications of thermal therapy with their challenges are first highlighted, especially with respect to treatment control and margins. Thereafter, it is quantitatively shown that clinically available thermometry fulfills the requirements and future research should focus on achieving better temperature control instead. With nanotechnology, novel strategies based on self-limiting nanoparticle systems and particle-based thermometers with active feedback control have also become available and are discussed. All of these approaches are systematically compared and analyzed with respect to their clinical applicability. The extent to which control over thermal therapy is necessary is also discussed alongside a presentation of the existing methods which fulfill the set requirements for clinical success and what issues remain to be tackled by research in the near future.

Fine Control of In Vivo Magnetic Hyperthermia Using Iron Oxide Nanoparticles with Different Coatings and Degree of Aggregation

“…NP0-D1 was the sample that exhibited the highest SAR value in water under 4 kA/m and 300 kHz (10 W/g). The 40 °C threshold, considered as a “safety temperature” [ 11 ], was overpassed only with NP0-D1 and NP3-D8. The latter had shown a lower SAR value in water (8 W/g) than NP0-D1 and it was necessary to increase the concentration of nanoparticles (1.8 to 4.5 mg of Fe per 100 mm 3 .…”

“…A similar behavior, with the tumor temperature rising after 2–3 min of increasing the voltage applied and decreasing after the voltage is lowered, can be observed in all experiments. The difficulty in controlling the rise of the temperature has been accurately described as one of the major drawbacks for the application of magnetic hyperthermia [ 11 ]. It is also observable in our results and also in the literature that variability in the heating rates of the tumors is high.…”

“…Another important issue for the clinical translation of magnetic hyperthermia is the poor control in real-time over the temperature increase once the AMF is activated. It is widely accepted that temperatures below 40 °C degrees are not harmful to tissues [ 11 , 12 ] whereas cells exposed to temperatures around 42 °C will undergo cell death mainly by apoptosis. This is what is known as mild hyperthermia, and it has been demonstrated that it has beneficial effects also by provoking structural changes in the tumor microenvironment and sensitizing cancer cells to radiotherapy and/or chemotherapy [ 13 ].…”

“…This is what is known as mild hyperthermia, and it has been demonstrated that it has beneficial effects also by provoking structural changes in the tumor microenvironment and sensitizing cancer cells to radiotherapy and/or chemotherapy [ 13 ]. However, if the temperature rises too much over 42 °C, a relatively larger number of cells will die by necrosis and irreversible damage can be caused to the surrounding healthy tissues [ 11 , 14 ]. One way of controlling the temperature in magnetic hyperthermia is the use of self-limiting NPs.…”

“…Average surface temperature increases of up to 7.8 ± 2.2 °C were measured when applying an AMF of 23.8 kA/m and 111 kHz, after intratumoral injection of magnetic nanocubes (0.7 mg of iron) [ 25 ]. However, the continuous recording of temperatures in specific spots might be difficult and the time required to reach a given temperature in the tumor is only rarely reported [ 11 ]. More insight on the temperature variations would help to better estimate the amount of NPs and the field conditions necessary to reach a therapeutic effect.…”