Hyperthermia | EPFL Graph Search

Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme temperature elevation occurs, it becomes a medical emergency requiring immediate treatment to prevent disability or death. Almost half a million deaths are recorded every year from hyperthermia. The most common causes include heat stroke and adverse reactions to drugs. Heat stroke is an acute temperature elevation caused by exposure to excessive heat, or combination of heat and humidity, that overwhelms the heat-regulating mechanisms of the body. The latter is a relatively rare side effect of many drugs, particularly those that affect the central nervous system. Malignant hyperthermia is a rare complication of some types of general anesthesia. Hyperthermia can also be caused by a traumatic brain injury. Hyperthermia differs from fever in that the body's temperature set point remains unchanged. The opposite is hypothermia, which occurs when the temperature drops below that required to maintain normal metabolism. The term is from Greek ὑπέρ, hyper, meaning "above", and θέρμος, thermos, meaning "heat". In humans, hyperthermia is defined as a temperature greater than , depending on the reference used, that occurs without a change in the body's temperature set point. The normal human body temperature can be as high as in the late afternoon. Hyperthermia requires an elevation from the temperature that would otherwise be expected. Such elevations range from mild to extreme; body temperatures above can be life-threatening. An early stage of hyperthermia can be "heat exhaustion" (or "heat prostration" or "heat stress"), whose symptoms can include heavy sweating, rapid breathing and a fast, weak pulse. If the condition progresses to heat stroke, then hot, dry skin is typical as blood vessels dilate in an attempt to increase heat loss. An inability to cool the body through perspiration may cause dry skin.

Perfluorinated HDAC inhibitors as selective anticancer agents

Paul Joseph Dyson, Tina Riedel

A series of potent histone deacetylase inhibitors is presented that incorporate alkyl or perfluorinated alkyl chains. Several new compounds show greater in vitro antiproliferative activity than the clinically approved inhibitor, SAHA. Furthermore, the new compounds show up to 5-fold greater activity against cancer cells than healthy cells. This selectivity is in contrast to SAHA, which is more active against the healthy cell line than the cancer cell line tested. Finally, we report an increase in activity for SAHA under mild hyperthermia, indicating that it could be an interesting candidate to use in combination with thermal therapy.

Royal Society of Chemistry2017

Iron oxide nanoparticles for diagnosis and therapy of lymph node metastases

Débora Bonvin

This thesis presents the synthesis, coating and characterization of iron oxide nanoparticles (IONPs) with properties especially designed for the ultimate simultaneous MRI detection and hyperthermia treatment of lymph node metastases, a combination called theranostics. This demanding aim requires to fulfill two different challenges at the same time: (i) synthesis of IONPs with exceptional properties for MRI and hyperthermia obtained with a synthesis method transferable to manufacturing facilities, and (ii) coating of IONPs with molecules, which simultaneously allow their dispersion and ideally have higher affinity to lymph node metastases than to other tissues. We therefore developed a novel simple aqueous method to synthesize IONPs by combining the standard co-precipitation method with a hydrothermal treatment. We studied the influence of the synthesis parameters, especially the hydrothermal treatment duration, on the IONPs' size, morphology, structure, crystallinity, as well as their magnetic, relaxometric and heating properties. As a result, we were able to control simultaneously the studied properties and to obtain IONPs with optimal properties for both MRI and hyperthermia. Subsequently, IONPs were coated in aqueous conditions with nine different molecules considered as biocompatible and non-toxic. In order to preserve the high relaxometric and heating properties of IONPs, we used small molecules to reduce the coating to a minimum. In that case, dispersion of IONPs with the chosen molecules were obtained by electrostatic stabilization. One of the major constraints was to obtain coated IONPs with hydrodynamic diameters smaller than 100 nm and with negative surface charges, both needed to access and be retained in the lymphatic system that is required for the targeting of lymph node metastases. In order to avoid to further enlarge the coating, we also used the available active groups of the coating molecules to target lymph node metastatic cells. In order to confirm the possibility to target such cells, we investigated the uptake of coated IONPs in four tumor cell lines from different cancer stages. Finally, the platform with optimal properties necessary for the targeting, detection and treatment of lymph node metastases was found to be IONPs coated with folic acid or adenosine triphosphate, which are targeting the prostate specific membrane antigen receptors or the highly metabolic nature of tumor cells, respectively. In the last part of this thesis, the interaction of IONPs with blood and lymph, especially the formation of the protein corona around IONPs, was investigated. Our study took into account the complex environment, which IONPs are subjected to in vivo. So far unconsidered in vitro conditions were examined, such as the dynamic variations of the flow or the transition of IONPs from one body fluid to the other.

EPFL2017

Correlating Magneto-Structural Properties to Hyperthermia Performance of Highly Monodisperse Iron Oxide Nanoparticles Prepared by a Seeded-Growth Route

Raffaella Buonsanti, Alessandro Genovese

Monodisperse cubic spinel iron oxide magnetic nanoparticles with variable sizes were prepd. following a multi-injection seeded-growth approach. As expected from such a known synthetic route, all samples were characterized by narrow size distributions, and showed excellent stability in both org. and aq. media without the presence of aggregates, thus becoming ideal candidates for the study of their hyperthermia performance. Specific Loss Power measurements indicated low heating powers for all samples without a max. for any specific size, contrary to what theory predicts. The magnetic study showed the formation of size-dependent nonsatd. magnetic regions, which enlarged with the particle size, evidencing a clear discrepancy between the crystal size and the effective magnetic vol. Strain map anal. of high resoln. transmission electron micrographs indicated the presence of highly strained crystal areas even if nanoparticles were monocryst. The origin of the crystal strain is strictly correlated with the seeded-growth synthetic procedure used for the prepn. of the nanoparticles, which turned out to alter their magnetic structure by creating antiphase boundaries. Considering the calcd. effective magnetic vols. and their magnetic dispersions in each sample, a reasonable agreement between hyperthermia expts. and theory was obtained.

2011

Iron oxide nanoparticles for diagnosis and therapy of lymph node metastases

Débora Bonvin

EPFL2017