Kshitij Kolhatkar, Prabir Patra, and Alicia Petryk's poster on the use of radiosensitization and hyperthermia in the treatment of cancer

Kolhatkar, Kshitij

Patra, Prabir

Petryk, Alicia

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Radiosensitization & Hyperthermia as Cancer Therapy Kshitij Kolhatkar, Prabir Patra, Alicia PetrykDepartment of Biomedical EngineeringUniversity of Bridgeport, Bridgeport, CTBackgroundRadiation therapy along with surgery and chemotherapy are the majortherapeutic strategies for cancer treatment. It involves the delivery ofhigh intensity ionizing radiation with high accuracy to the tumor tissueresulting in the death of tumor cells. Radiation sensitization is aprocess of enhancing the susceptibility of tumor tissues to injury byradiation exposure. Hence, radiosensitizers are therapeutic or otherwiseinert agents that enhance the effects of radiation therapy.1Hyperthermia (also called thermal therapy or thermotherapy) is a typeof cancer treatment in which body tissue is exposed to hightemperatures (up to 45°C). Hyperthermia is almost always used withother forms of cancer therapy, such as radiation therapy andchemotherapy. Hyperthermia may make some cancer cells moresensitive to radiation or harm other cancer cells that radiation cannotdamage. When hyperthermia and radiation therapy are combined, theyare often given within an hour of each other. Hyperthermia can alsoenhance the effects of certain anticancer drugs. Magnetic nanoparticles(MNP) can induce localized hyperthermia when exposed to analternating magnetic field (AMF).3,4References1. Kwatra, D., Venugopal, A., & Anant, S. (2013). Nanoparticles in radiation therapy: a summary of various approaches to enhance radiosensitization in cancer. Translational Cancer Research, 2(4), 330–342. https://doi.org/10.21037/15502. M Hidayatullah, N. and W. S. B. (2016). ZnFe2O4 nanoparticles for potential application in radiosensitization. IOP, 6. https://doi.org/10.1088/1742-6596/694/1/0120283. van der Zee J. Heating the patient: a promising approach? Annals of Oncology 2002; 13(8):1173–1184.4. Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia. Critical Reviews in Oncology/Hematology 2002; 43(1):33–56.5. Klein S, Sommer A, Distel LV, Neuhuber W, Kryschi C. Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation. Biochemical and biophysical research communications. 425(2): 393-397, 2014.6. Petryk, Alicia Ailie. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy. Thesis. 2013. Dartmouth College, Hanover, NH, Print.Quantum dots as Radiosensitizers: The mechanism of action for these is based on the principle of generation of radicals upon absorption of visible light by the quantum dots. Since these light waves have much less toxicity as compared X-rays or gamma rays, the overall adverse effects of the therapy are greatly reduced. The major disadvantage of this approach is that light waves within the visible spectrum have very little penetration depth and hence the therapies designed utilizing these mechanisms will be suitable only for superficial cancers.1Gold Nanoparticles: Gold is biocompatible and it enhances the effect of the radiation over a large area of tumor thus eliminating the need of the nanoparticles to be delivered to all the cells of the tumor tissue. It is much easier to perform overall and tissue specific pharmacokinetic studies with the gold nanoparticles as they are easy to image and quantify. Thus the dose levels can be optimized for best results.1ZnFe2O4 Nanoparticle: Zinc-iron oxide particles have an effective atomic number higher than the effective atomic number of the body's tissues. When used as a radiosensitizer, these nanoparticles showed increase in absorbed dose and increase in radiation effect of the therapy.2Fe3O4 Nanoparticles: Magnetic nanoparticles  are promising materials for hyperthermia treatment, as well as radiation sensitizing agents. Relative to other nanoparticles considered for radiation sensitization, they are highly biocompatible, and well suited for adjuvant hyperthermia applications.6Figure 1: Summary of various approaches for enhancing the radiosensitization in cancer cells (top). Possible radiation interactions with high Z materials (bottom). .Hypothesis: the addition of MNP to ionizing radiation increases the production of reactive oxygen species (ROS).By increasing the DNA damage due to ROS, MNP have the potential to potentiate local radiation. Whether ROS production is increased by the presence of MNP will be examined through in vitro studies which utilize the Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay to measure the changes in ROS due to the presence of MNP.7 Related to this concept, is the question whether intracellular vs. extracellular MNP are more effective at generating cytotoxicity. Significant efforts have been made to increase the intracellular nature of MNP as a means of inducing intracellular heating with AMF exposure. Whether there are significant benefits or differences resulting from intracellular heating remain unresolved in the field. Furthermore, the difference in cytotoxicity of intracellular vs. extracellular MNP combined with radiation is also not understood. Variables will include not only intracellular vs. extracellular MNP, but cell density (pelleted vs. isolated plated cells), and radiation type and energy. Finally, the addition of AMF induced heating will also be included to determine its effect on both the achieved cytotoxicity and ROS levels.5(Kwatra 2013)(Kwatra 2013)Figure 2: Transmission electron microscopy image of MNP located within an MTGB mouse mammary adenocarcinoma cell, following intratumoral injection. The clustering and intracellular uptake near nucleus may enhance the cytotoxicity of radiation therapy.

Radiosensitization & Hyperthermia as Cancer Therapy

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Radiosensitization & Hyperthermia as Cancer Therapy

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