Study of the effect of ceramic Ta2O5 nanoparticle distribution on cellular dose enhancement in a kilovoltage photon field

McKinnon, Sally; Engels, Elette; Tehei, Moeava; Konstantinov, Konstantin; Corde, Stéphanie; Oktaria, Sianne; Incerti, S.; Lerch, Michael L. F; Rosenfeld, Anatoly B.; Guatelli, Susanna

doi:10.1016/j.ejmp.2016.09.006

Cited by 21 publications

(21 citation statements)

References 23 publications

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“…Thicker shells produce more secondary electrons in the NP, however, at the same time, the number of electrons escaping the NP reduces because of the higher probability of ionisation interactions, which increase electron absorption in the NP itself. The interplay between the two effects leads to an increase in DER, but the DER increase becomes less efficient, eventually reaching a saturation effect as described in McKinnon et al [29].…”

Section: ) Statistical Uncertainty Is Present Though Smaller Than mentioning

confidence: 90%

“…The details of the radiobiological experiments will be object of a separate article. Ta 2 O 5 NPs are nano-structured ceramic particles that have shown to enhance conventional kV and MV radiotherapy [29,30]. Ta 2 O 5 NPs are manufactured according to Brown et al [28] and added to the cell culture flask to incubate for 24 hours.…”

Section: Motivation Of the Geant4 Simulation Study: Experimental Measmentioning

confidence: 99%

“…High-Z nanoparticles (NPs) have been shown to improve the effectiveness of dose conformity to tumour tissue in the case of conventional unsegmented kilovoltage X-rays [19][20][21][22][23][24][25][26][27][28][29][30]. The advantages of NPs, besides the primary benefit of enhancing tumour radiosensitivity, often include biocompatibility, permeability to cell membranes due to their nano-scale dimensions, ability to specifically target certain tumours when coated and actively accumulate at tumour sites with leaky vasculature [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…These nanostructured ceramic particles have different aggregation properties than inert metal NPs. In particular, they tend to form shell aggregates instead of distributing homogeneously in the medium, producing different physical dose enhancements [29].…”

Section: Introductionmentioning

confidence: 99%

“…Geant4 simulations were performed by McKinnon et al [29] to characterise the physical dose enhancement produced by different distributions of Ta 2 O 5 , as observed experimentally, for a 150 kVp broad beam. The shell structures produced large localised physical dose enhancements to surrounding cells using the kV broad beam, with large NP clusters up to 7 µm thick producing dose enhancement that is up to 100 times.…”

Section: Introductionmentioning

confidence: 99%

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Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

et al. 2016

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Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue sparing with spatially fractionated kilovoltage X-ray microbeams through the dose volume effect. Experimental measurements with Ta 2 O 5 nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. Ta 2 O 5 NPs were observed to form shells around cell nuclei which may be the reason for their efficiency in MRT. In this article, our experimental observation of NP shell formation is the basis of a Geant4 radiation transport study to characterise dose enhancement by Ta 2 O 5 NPs in MRT. Our study showed that NP shells enhance the physical dose depending microbeam energy and their location relative to a single microbeam. For monochromatic microbeam energies below ∼70 keV, NP shells show highly localised dose enhancement due to the short range of associated secondary electrons. Low microbeam energies indicate better targeted treatment by allowing higher microbeam doses to be administered to tumours and better exploit the spatial fractionation related selectivity observed with MRT. For microbeam energies above ∼100 keV, NP shells extend the physical dose enhancement due to longer-range secondary electrons. Again, with NPs selectively internalised, the local effectiveness of MRT is expected to increase in the tumour. Dose enhancement produced by the shell aggregate varied more significantly in the cell population, depending on its location, when compared to a homogeneous NP distribution. These combined simulation and experimental data provide first evidence for optimising MRT through the incorporation of newly observed Ta 2 O 5 NP distributions within 9L cancer cells. Disciplines Engineering | Science and Technology Studies Publication DetailsEngels, E., Corde, S., McKinnon, S., Incerti, S., Konstantinov, K., Rozenfeld, A., Tehei, M., . Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam activated radiation therapy. Physica Medica: an international journal devoted to the applications of physics to medicine and biology, 32 (12)

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Section: ) Statistical Uncertainty Is Present Though Smaller Than mentioning

confidence: 90%

Section: Motivation Of the Geant4 Simulation Study: Experimental Measmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

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Quantification of gold nanoparticle photon radiosensitization from direct and indirect effects using a complete human genome single cell model based on Geant4

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To investigate the radiosensitization properties of gold nanoparticles (GNPs) and better understand the intricate deoxyribonucleic acid (DNA) damage induction mechanisms involved in GNP-aided radiotherapy, a single cell model with complete human genome based on the Geant4 Monte Carlo toolkit was applied. Materials and methods: A Geant4-DNA model was implemented to simulate direct and indirect DNA damage generated in the physical and chemical stages. In the physical stage, a mixed-physics approach was taken by using Geant4-DNA in water and Livermore in gold. Water radiolysis was created posteriorly in the physicochemical and chemical stages to simulate indirect damage from reactions between DNA molecules and OH• radicals. A mono-energetic photon beam (100 keV) and two clinical photon sources (250-kVp, 6-MV flattening-filter free) were simulated for modeling the irradiation of a single cell with or without GNPs. In order to study the effects of GNP size on radiosensitization, 15, 30, and 100 nm GNPs were simulated. The effects of intracellular distribution were simulated using 90-nm GNPs with different characteristics of distribution within the cell. The time dependence of DNA damage enhancement was also studied with chemistry stage simulation end-time no larger than 10 ns. Results: Double strand break (DSB) enhancement due to direct and indirect action was quantified under different scenarios. Under realistic cellular uptake condition, the 100-nm GNPs had the most significant increase in DSBs: 40.9% and 28.5% for 100 keV and 250-kVp photon irradiation, respectively. The intracellular localization showed differing levels of radiosensitization with a maximum of 64%, 27%, and 6% DSB enhancements for 100 keV, 250-kVp, and 6-MV respectively, when 90-nm GNPs congregate around the nucleus. Conclusion:The results indicate that photon energy, GNP size, and intracellular distribution play an important role in the enhancement of DSB from direct and indirect damage under scenarios close to cell experiments. The radiosensitization effects due to indirect damage are significant and should be considered carefully.

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X-ray sensitive high-Z metal nanocrystals for cancer imaging and therapy

et al. 2021

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Study of the effect of ceramic Ta2O5 nanoparticle distribution on cellular dose enhancement in a kilovoltage photon field

Cited by 21 publications

References 23 publications

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

Quantification of gold nanoparticle photon radiosensitization from direct and indirect effects using a complete human genome single cell model based on Geant4

X-ray sensitive high-Z metal nanocrystals for cancer imaging and therapy

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