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Local hyperthermia cancer treatment studies using a new temperature-imaging-hyperthermia-microscopy instrument

Periodic Reporting for period 1 - HYPTEMPCELL (Local hyperthermia cancer treatment studies using a new temperature-imaging-hyperthermia-microscopy instrument)

Reporting period: 2018-09-01 to 2020-08-31

One of the main challenges in current human health research concerns the treatment of cancer. Indeed, cancer remains one of the main causes of death in the developed countries, which has a significant cost both humanly and economically speaking. A large wide of treatments are actually in development, and several present good results and may be available in several hospitals in Europe. Among them, one treatment which proved as promising is magnetic cancer hyperthermia therapy. That consists in the injection of nanoparticles which are able to heat when submitted to an ac magnetic field, killing preferentially the cancer cells instead of the healthy cells due to a difference in temperature sensitivity. However, the main inconvenient of the technique arises from the concept itself. The heating power of the current nanoheaters is relatively low, which requires a massive and direct injection in the tumor. Moreover, the control of the temperature is ensured by inserting thermocouple i.e macroscopic thermometers directly in the tissues adjacent to the tumor, which is quite invasive.
The idea of the current project to solve these inconveniences consists in designing a softer approach based on local intracellular heating. Concretely, that consists to consider this treatment not at the tumor scale but directly at cells’ scale. That implies to internalized the nanoheaters inside the cancer cells using appropriate targeting agents before to produce the heating, which may lead to their death. Moreover, the control of the temperature at such scale may be provided by a unique tool developed here. By using a molecular luminescent thermometer, we may be able to sense the local temperature directly in the cancer cells with high precision and fast response, and without being invasive.
Consequently, the currents objectives of the project consists in 1) developing a system to image the temperature in 2D and to couple it to a magnetic induction system which can be apply to cell cultures under microscope observation, 2) to observe the diffusion of the heat produced by the nanoheaters into the cells and 3) to determine if such temperature increase is able to provoke cells death. All these objectives may permit to determinate the feasibility of a hyperthermia therapy based on local intracellular heating as new advanced cancer therapy.
The first part of the work has consisted to improve the efficiency of the luminescent thermometer by studying a series of different compounds susceptible to be used. That has implied their synthesis, characterization and the study of their luminescent properties. Different potential candidates have been selected and will be incorporated to the nanoheaters to be tested, to evaluate first their efficiency to sense temperature and then their stability in living media, which may be one of the critical parameters. The systems which would be satisfying these criterions would be internalized to cancer cells and measurements of the heat diffusion would be performed.
Another part of the work concerns the elaboration of a system to measure the temperature under applying a magnetic field coupled with a microscope.
One of the main results expected until the end of the project concerns the estimation of the cell heat conductivity. If we succeed to determine how the temperature propagates in the cell, that may permit to a better understanding of the process happening at cell scale level, and may improve the current models used to treat cancer by hyperthermia.
On other hand, if the method proves to be able to kill cancer cells, that would pave the way to the development of a new therapy more efficient and less invasive to cure cancer. In such case, that would permit a better chance to cure cancer, improving patient life and creating a new economical field in public health.
This may be enforced by the development of the tool permitting the sensing of the temperature under magnetic heating which can be coupled to a microscope. Such device may be used in labs and hospitals.
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