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Using Gold Nanoparticles to Target Mitochondria in Radiation Therapy

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A McNamara

A McNamara1*, S McMahon2 , Y Lin3 , H Paganetti4 , Z Kuncic5 , J Schuemann6 , (1) Massachusetts General Hospital & Harvard Med. Sch., Boston, MA, (2) Massachusetts General Hospital, Boston, Ma, (3) Massachusetts General Hospital and Harvard Medical School, Boston, MA, (4) Massachusetts General Hospital, Boston, MA, (5) University of Sydney, Sydney, NSW, (6) Massachusetts General Hospital, Boston, MA


TU-G-CAMPUS-T-14 (Tuesday, July 14, 2015) 5:30 PM - 6:00 PM Room: Exhibit Hall

Purpose: The mitochondrion, like the cell nucleus, contains genetic material and plays several critical roles that determine the cell viability, including neutralization of free radicals within the cell. Studies have shown that irradiated cells with impaired mitochondria will incur more damage to the cell nucleus. This study investigates the potential use of GNPs to enhance radiation-induced damage to the organelle.

Methods: The compositions of the organelles of a JURKAT cell were determined experimentally. Using Monte Carlo simulations, we investigate the significance of dose enhancement in a monoenergetic (10 - 50 keV and 6 MeV) x-ray irradiated cell cytoplasm, consisting of the experimentally determined composition. We also investigate the track structure of secondary electrons in the mitochondria using Geant4-DNA in the presence and absence of GNPs for incident protons and photons. The biological effect was determined using an approach based on the local effect model, assuming the mitochondrial DNA (mtDNA) was the primary target.

Results: Adding 0.01% of gold to the cell cytoplasm material can cause substantial dose enhancement, dependent on the incident x-ray energy. Track structure Monte Carlo (MC) simulations show an increased number of ionization events within the mitochondrion structure. The close proximity of GNPs to the mtDNA storing nucleoid may cause the mtDNA to receive doses above ~100 Gy for keV x-rays, leading to mitochondrial dysfunction.

Conclusion: A substantial increase in ionization events can occur in the mitochondria in the presence of GNPs. If GNPs can be delivered to tumors and attached to a sufficient number of mitochondria inside the tumor cells, mitochondrial induced cell death could be a prevalent cause of cell death. The biological structures developed here will be included in the biological MC toolkit, TOPAS-nBio.

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