349934 Radiosensitization in the Treatment of Lung Cancer Via Hyperthermia, Iron Oxide Nanoparticles, and Gold Nanoparticles

Monday, November 4, 2013
Grand Ballroom B (Hilton)
Michelle Pressly1, Anastasia Kruse1, Samantha A. Meenach2, Kimberly Anderson1 and J. Zach Hilt1, (1)Chemical and Materials Engineering, University of Kentucky, Lexington, KY, (2)Chemical Engineering, University of Rhode Island, Kingston, RI

Lung cancer for both men and women is the number-one cause of cancer deaths with survival rates of less than 16 % at five years (1).  Over half of cancer patients receive radiation at some point during treatment (2). Radiosensitizing treatments, treatments that enhance radiation, are particularly relevant in combating cancer because they increase the damage to cancer tissue while limiting the damage to surrounding normal tissue. If radiosensitizing treatments can be targeted to cancer cells, this will make radiation less harmful to the healthy tissue and concentrate the radiation therapy at the tumor site. In this research, three different possible radiosensitizers were studied in vitro: hyperthermia, iron oxide nanoparticles, and gold nanoparticles on two different lung cancer cell lines.

Hyperthermia is defined as the heating of cells/tissue up to 45°C (3). The combination of radiation and hyperthermia has been shown to improve the clinical response when compared to treatment with radiation alone. It has been shown in vitrothat the enhancement of radiation damage by heat generally occurs in all cell types. Higher temperatures, longer exposure times and heating directly prior to or during radiation are associated with more cell death (4).   Gold nanoparticles have been shown to enhance radiation. Due to the high atomic number (Z=79) of gold, outer electrons are easier to excite due to their distance from the nucleus of the atom and when they are excited and emit photons, this energy can be absorbed by nearby cells and cause damage (5).  Iron oxide nanoparticles are thought to work as a radiosensitizer as internalized iron oxide nanoparticles have been shown to increase reactive oxygen species (ROS) formation. This increase in ROS enhances radiation effects and causes more cell death (6).  Two different types of lung cancer, epithelial lung carcinoma (A549) and bronchioalveolar carcinoma of the lung (H358) were chosen due to radiosensitizing effects being cell dependent (7). Comparing the effects of each type of treatment on these types of cancer will help bridge the gap between any one of the treatments and further trials. In these studies, hyperthermia showed promising results by significantly lowering both cell number and surviving fraction when two hour hyperthermia was combined with radiation in both lung cancer lines. The gold nanoparticles did not show enhancement effects in combination with radiation at the concentrations tested (up to 10 nM).  The citrate coated iron oxide nanoparticles (up to 100mM), which were used in these studies, were very unstable in cell culture media and resulted in significant toxicity to the cells resulting in no enhancement effect in combination with radiation. The hypothesis is that, after further optimization of concentration of gold and iron oxide nanoparticles, these methods of radiosensitizing will show enhancing results similar to that of hyperthermia.

This research was a part of the University of Kentucky Research Experience for Undergraduates Program funded by the National Science Foundation and the University of Kentucky Bucks for Brains Program.

(1) Lung Cancer Symptoms, Stages, Survival, Statistics, Treatment, Types - MedicineNet."MedicineNet. N.p., n.d. Web.

(2) "Lung Cancer Treatment Statistics and Results." NSCLC Lung Cancer Survival Statistics. Cancer Treatment Centers of America, Web.

(3) "National Cancer Institute." Hyperthermia in Cancer Treatment -. N.p., n.d. Web.

(4) Burdett, E., et al. (2010). Tissue Engineering: Part B 16(3): 351-359.

(5) Asghar Mesbahi, A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer, Reports of Practical Oncology & Radiotherapy, Volume 15, Issue 6, November–December 2010, Pages 176-180.

(6) Stefanie Klein, Anja Sommer, Luitpold V.R. Distel, Winfried Neuhuber, Carola Kryschi, Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation, Biochemical and Biophysical Research Communications, Volume 425, Issue 2, 24 August 2012, Pages 393-397

(7) Lartigau E, Guichard M. Does tirapazamine (SR-4233) have any cytotoxic or sensitizing effect on three human tumour cell lines at clinically relevant partial oxygen pressure? Int J Radiat Biol. 1995 Feb;67(2):211–216.


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