Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol

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dc.contributor.authorMcNamara, ALen_AU
dc.contributor.authorKam, WWYen_AU
dc.contributor.authorScales, Nen_AU
dc.contributor.authorMcMahon, SJen_AU
dc.contributor.authorBennett, JWen_AU
dc.contributor.authorByrne, HLen_AU
dc.contributor.authorSchuemann, Jen_AU
dc.contributor.authorPaganetti, Hen_AU
dc.contributor.authorBanati, RBen_AU
dc.contributor.authorKuncic, Zen_AU
dc.date.accessioned2020-03-26T03:42:41Zen_AU
dc.date.available2020-03-26T03:42:41Zen_AU
dc.date.issued2016-07-20en_AU
dc.description.abstractGold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies  ~70 eV, substantially lower than that of liquid water  ~78 eV. Monte Carlo simulations for 10–50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of  ~1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol. © 2016 Institute of Physics and Engineering in Medicineen_AU
dc.identifier.citationMcNamara, A. L., Kam, W. W. Y., Scales, N., McMahon, S. J., Bennett, J. W., Byrne, H. L., Schuemann, J., Paganetti, H., Banati, R. B., & Kuncic, Z. (2016). Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol. Physics in medicine and biology, 61(16), 5993-6010. doi:10.1088/0031-9155/61/16/5993en_AU
dc.identifier.govdoc9009en_AU
dc.identifier.issn0031-9155en_AU
dc.identifier.issue16en_AU
dc.identifier.journaltitlePhysics in medicine and biologyen_AU
dc.identifier.pagination5993-6010en_AU
dc.identifier.urihttps://doi.org/10.1088/0031-9155/61/16/5993en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9252en_AU
dc.identifier.volume61en_AU
dc.language.isoenen_AU
dc.publisherIOP Publishingen_AU
dc.subjectMitochondriaen_AU
dc.subjectNanoparticlesen_AU
dc.subjectCytoplasmen_AU
dc.subjectRadiotherapyen_AU
dc.subjectGolden_AU
dc.subjectMonte Carlo Methoden_AU
dc.subjectCell constituentsen_AU
dc.subjectCell nucleien_AU
dc.titleDose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosolen_AU
dc.typeJournal Articleen_AU
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