Radiation Biology

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SU_42_2428 - Determining the Precise Enhancement Factor for Gold Nanoparticle Radiosensitization

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Determining the Precise Enhancement Factor for Gold Nanoparticle Radiosensitization
S. V. Jenkins1, R. J. Griffin2, and M. Borrelli1; 1UAMS, Little Rock, AR, 2University of Arkansas for Medical Sciences, Little Rock, AR

Purpose/Objective(s): Nanoparticles, particularly those made of high Z materials like gold or hafnium have shown some promise in radiosensitization approaches in murine models and clinical trials. The results, however, are largely phenomenological and lack mechanistic detail. There is general evidence that a close association between particles and the cell increases radiosensitization. To better understand the true mechanism and potency, gold nanocages were coated on glass coverslips to control the number of nanoparticles contacting each cell membrane but not interacting with the nucleus, enabling precise determination of a dose enhancement factor (DEF).

Materials/Methods: Gold nanocages of ~50 nm edge length were synthesized via galvanic replacement of a sacrificial silver nanocube template. These nanocages were then attached to glass coverslips that had been treated with (3-mercaptopropyl)trimethoxysilane. Following deposition the surfaces were sterilized, and 4T1 murine breast tumor cells were seeded on the surface and allowed to adhere. This model system was then treated with 4 Gy of radiation (150 keV source), and colony formation was assessed after 8 days. Cell size was measured using optical microscopy. Electron trajectories were simulated in water (CASINO software) with an electron energy max of 50 keV.

Results: Surfaces were coated at densities of 0, 17, 34, or 68 AuNC/μm2. The cell contact area averaged 308 +/- 15 μm2, indicating an average of 0, 0.52, 1.04, or 2.08 x 104 AuNC contacting each cell +/- 5%. Increasing concentration of AuNC was found to significantly enhance radiosensitization with a maximal dose enhancement factor of 2.25 occurring at the 68 AuNC/μm2 density. Interestingly, we observed a linear relationship between dose enhancement and number of AuNCs, with ~15,000 AuNCs/cell giving a DEF of 2. Electrons generated from the particle upon interaction with the irradiation photons were predicted travel a max of ~60 µm with a 50 keV initial energy, indicating the electrons can pass completely through 4T1 cells with an average diameter of 10-20 µm while still maintaining enough energy to create biologically relevant collisions.

Conclusion: Gold nanocages were found to provide significant radiosensitization in an in vitro model. Initial results indicate that a particle density and sensitization are linearly related, and the electrons from nanocages on the surface of the cell affect membrane, cytosol and nuclear compartments. We are working to compare dose enhancement caused by distinct gold spheres, rods, or pyramids, and materials such as carbon, iron oxide, hafnium oxide, and silica. The distance between the nucleus and surface will be increased with a polymer layer to quantitatively assess the relative contribution of membrane vs. DNA damage in cell killing, which will also be measured through manipulation of the cell cycle.

Author Disclosure: S.V. Jenkins: None. R.J. Griffin: Past President; Society for Thermal Medicine. Board Member; American College of Cryosurgery.

Robert Griffin, PhD

Disclosure:
Employment
University of Arkansas for Medical Sciences: Professor: Employee

Ownership
IGF Oncology: Stock Options

Leadership
American College of Cryosurgery: Board Member

Biography:
Robert J. Griffin, PhD, is a Professor of radiation and cancer biology in the Department of Radiation Oncology at the University of Arkansas for Medical Sciences with over 20 years of experience in peer-reviewed research. Much of his work has been studying the interactions of normal and tumor microvasculature with tumor cells, blood flow, hypoxia and the general role of the tumor microenvironment in driving metabolism and proliferation. Exploiting aspects of the tumor microenvironment to improve response to radiation, thermal treatment, or chemotherapy while maintaining a beneficial therapeutic ratio is the ultimate goal of studies in his research group. He has acted as President and program chair for the Society for Thermal Medicine, which has an emphasis on nanotechnology and radiosensitization using a variety of modalities. He is active on the program committee for the ASTRO refresher course and the Radiation Research society as well as on the annual meeting and scientific and educational program development committee for ASTRO. Currently, he is also associate senior editor for biology for the Red journal as well as radiation therapy section editor for the journal Technology in Cancer Research and Treatment.

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