3.3.1. Biological Aspects of Hyperthermia

Tumoral tissues potentially contain necrotic, hypoxic, and low pH areas rendering them resistant to chemotherapy and radiotherapy. Moreover, cells in late phase S (Synthesis i.e., DNA replication) are usually more radioresistant than cells in the M phase (Mitosis) but sensitive to heat [94]. In this context, hyperthermia in conjunction with conventional therapies such as chemotherapy drugs or radiotherapy brings a synergistic therapeutic effect [53] and potentially improves tumoral regression [94]. The therapeutic effect of hyperthermia relies on the fact that cancer cells are more sensitive to heat because of their increased metabolic rate [53]. The exposition of cancer cells to a 40–46 ◦C temperature induces a thermal shock modifying cellular processes, altering the structure and function of proteins and ultimately promoting apoptosis of exposed cells. In addition, heat stress restores blood flow, permeability, pH, and oxygenation of the tumor microenvironment [53,73] and inhibits the repair of ionizing radiation-induced DNA damage [48]. Moreover, MHT may induce effective and genuine immunogenic tumor cell death as recently demonstrated [95]. MHT is the main hyperthermal strategy currently being developed for therapeutic applications. An optimal hyperthermia treatment allows a high heating efficiency, in a short time, and with a minimum concentration to avoid systemic side effects [54].
