Determining dose enhancement factors of high-Z nanoparticles from simulations where lateral secondary particle disequilibrium exists

Rabus, Hans; Gargioni, E.; Li, Wei Bo; Nettelbeck, Heidi; Villagrasa, C.

doi:10.1088/1361-6560/ab31d4

Cited by 26 publications

(36 citation statements)

References 43 publications

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“…If this underestimation is corrected for, it will significantly decrease the dose enhancement factor. A quantitative reduction of DER by applying a real source geometry in simulation will be estimated by another work [64]. (2) Due to the confined beam used in the simulation, the contribution of Compton or Rayleigh scattered photons interacting with the nanoparticle is underestimated.…”

Section: Limitation Of the Present Simulationsmentioning

confidence: 99%

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

Belchior

Beuve

et al. 2020

Physica Medica

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Section: Limitation Of the Present Simulationsmentioning

confidence: 99%

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

Belchior

Beuve

et al. 2020

Physica Medica

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“…11,14,22,26 However, the enhancement is reduced at larger spatial scales when considering dose to water from the incident proton beam as well as the electrons emitted from the nanoparticle and secondary electron equilibrium effects. 35,36 The use of integrated enhancement factors provided a representative value for direct comparison of the evaluated nanoparticle geometries.…”

Section: Reactionmentioning

confidence: 99%

Gold nanoparticle enhanced proton therapy: A Monte Carlo simulation of the effects of proton energy, nanoparticle size, coating material, and coating thickness on dose and radiolysis yield

et al. 2019

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Purpose Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the tumor. Proton therapy offers improved sparing of tissue distal of the tumor along the beam path and reduced integral dose compared to conventional photon therapy. The combination of proton therapy with radiosensitizers offers the potential for an enhanced therapy with increased effect within the tumor and low integral dose. The simulations performed in this work determine the effect of nanoparticle characteristics and proton energy on the nanoscale dose and radiolysis yield enhancement for a single gold nanoparticle irradiated with a proton beam. This data can be used to determine optimal nanoparticle characteristics to enhance proton therapy. Methods A two‐stage Monte Carlo simulation was performed using Geant4. In the first stage of the simulation, the physical interactions of protons within a gold nanoparticle were modeled and the secondary electrons escaping the nanoparticle's surface were scored in a phase space file. In the second stage of the simulation, the phase space file was used as an input to model the physical interactions of the secondary electrons in water and the resulting production and chemical interactions of reactive species. By comparing a gold nanoparticle with an equivalent water nanoparticle, the nanoscale enhancement of dose and radiolysis yield was calculated. Results A large nanoscale enhancement of both the dose and radiolysis yield of up to a factor of 11 due to gold nanoparticles was found for most simulated conditions. For 50 nm gold nanoparticles, a large enhancement factor of 9–11 was observed for high proton energies; however, the enhancement was reduced for proton energies below 10 MeV. For 5 MeV incident protons, it was found that the enhancement factor was approximately 9 for gold nanoparticles of sizes 5–25 nm with a reduction in enhancement observed for nanoparticle sizes outside this range. Additionally, it was found that larger nanoparticle sizes resulted in greater total energy deposition and radiolysis yields per proton flux but with reduced efficiency per nanoparticle mass. It was observed that a large loss of enhancement occurred for thick nanoparticle coatings. However, for polyethylene glycol (PEG) coatings, coating density had a minimal effect on enhancement. Conclusions A large enhancement in dose and radiolysis yield was observed. However, the low‐energy secondary electrons produced within the gold for lower energy protons are susceptible to self‐absorption and result in the loss of enhancement observed for larger nanoparticles and thicker coatings. The radiolysis yield and dose increase with nanoparticle size; however, the yield and dose per gold mass decrease due to self‐absorption. Therefore, an intermediate nanoparticle size of approximately 10–25 nm maximizes both the radiolysis yield and dose as well as the enhancement. Coatings should be kept to the minimum effective thickness to limit ...

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“…The Dose-Enhancement Factor (DEF) reflects the additional contribution of irradiated PtNP to the secondary electron emission, as compared to the secondary electron emission after water irradiation alone. Thus, when calculating the DEF, this energy deposition ( Figure 7 B) must be taken into account, as there is a risk of overestimating this factor if it is not considered [ 13 ]. All the particles described above—both primary and secondary electrons—interact with the nanoparticles, and the resulting additional electrons that escape from the nanoparticle are thus those that will have a potential enhancement effect.…”

Section: Resultsmentioning

confidence: 99%

“…The main peak, linked to the Auger emission, has a very low range. It has recently been reported [ 13 ] that, without taking into account the electron balance, i.e., when the beam of particles arriving in the nanoparticle has a size equivalent to the size of the nanoparticle, the DEF is very largely overestimated. In our study, the overestimation reaches a factor of 10.…”

Section: Resultsmentioning

confidence: 99%

“…It is important to remember that the DEF calculation method can induce a significant bias if the electronic equilibrium is not considered [ 13 ]. The three steps in which the simulation was performed, described in the material and methods section, allowed us to obtain the needed electronic equilibrium and preserve the needed statistics for the number of simulated interactions with NPs.…”

Section: Discussionmentioning

confidence: 99%

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Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses

Hullo

Grall

Perrot

et al. 2021

IJMS

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High-Z metallic nanoparticles (NPs) are new players in the therapeutic arsenal against cancer, especially radioresistant cells. Indeed, the presence of these NPs inside malignant cells is believed to enhance the effect of ionizing radiation by locally increasing the dose deposition. In this context, the potential of platinum nanoparticles (PtNPs) as radiosensitizers was investigated in two breast cancer cell lines, T47D and MDA-MB-231, showing a different radiation sensitivity. PtNPs were internalized in the two cell lines and localized in lysosomes and multivesicular bodies. Analyses of cell responses in terms of clonogenicity, survival, mortality, cell-cycle distribution, oxidative stress, and DNA double-strand breaks did not reveal any significant enhancement effect when cells were pre-exposed to PtNPs before being irradiated, as compared to radiation alone. This result is different from that reported in a previous study performed, under the same conditions, on cervical cancer HeLa cells. This shows that the efficacy of radio-enhancement is strongly cell-type-dependent. Simulation of the early stage ionization processes, taking into account the irradiation characteristics and realistic physical parameters in the biological sample, indicated that PtNPs could weakly increase the dose deposition (by 3%) in the immediate vicinity of the nanoparticles. Some features that are potentially responsible for the biological effect could not be taken into account in the simulation. Thus, chemical and biological effects could explain this discrepancy. For instance, we showed that, in these breast cancer cell lines, PtNPs exhibited ambivalent redox properties, with an antioxidant potential which could counteract the radio-enhancement effect. This work shows that the efficacy of PtNPs for enhancing radiation effects is strongly cell-dependent and that no effect is observed in the case of the breast cancer cell lines T47D and MDA-MB-231. Thus, more extensive experiments using other relevant biological models are needed in order to evaluate such combined strategies, since several clinical trials have already demonstrated the success of combining nanoagents with radiotherapy in the treatment of a range of tumor types.

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Determining dose enhancement factors of high-Z nanoparticles from simulations where lateral secondary particle disequilibrium exists

Cited by 26 publications

References 43 publications

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

Gold nanoparticle enhanced proton therapy: A Monte Carlo simulation of the effects of proton energy, nanoparticle size, coating material, and coating thickness on dose and radiolysis yield

Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses

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