The Dichotomous Nature of Dose Enhancement By Gold Nanoparticle Aggregates in Radiotherapy

Gadoue, Sherif M.; Zygmanski, Piotr; Sajo, Erno

doi:10.2217/nnm-2017-0344

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…Radiation dose enhancement has been reported also for other metal-containing NPs, including platinum, [171] iridium, [172] selenium [173] Fe-Pt clusters, [174] superparamagnetic iron oxide, [175] as well as gadolinium MRI-contrast agents, [176] as reviewed by Liu et al [177] In addition to the effect of high Z, NP aggregation is able to produce hot spots of dose enhancement. [178] The dose enhancement is LETdependent, being higher at low X-ray energies, [179,180] such LETdependent radiosensitization with Au NPs has been reported by Li et al [181]…”

Section: Dose Partitioningmentioning

confidence: 82%

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

et al. 2020

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Engineered nanomaterials that produce reactive oxygen species on exposure to X‐ and gamma‐rays used in radiation therapy offer promise of novel cancer treatment strategies. Similar to photodynamic therapy but suitable for large and deep tumors, this new approach where nanomaterials acting as sensitizing agents are combined with clinical radiation can be effective at well‐tolerated low radiation doses. Suitably engineered nanomaterials can enhance cancer radiotherapy by increasing the tumor selectivity and decreasing side effects. Additionally, the nanomaterial platform offers therapeutically valuable functionalities, including molecular targeting, drug/gene delivery, and adaptive responses to trigger drug release. The potential of such nanomaterials to be combined with radiotherapy is widely recognized. In order for further breakthroughs to be made, and to facilitate clinical translation, the applicable principles and fundamentals should be articulated. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy. A roadmap for designing nanomaterials with optimized anticancer performance is also shown and the potential clinical significance and future translation are discussed.

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Section: Dose Partitioningmentioning

confidence: 82%

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

et al. 2020

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“…The photon source was modeled using a parallel plane source with beam width that covers the entire cell. This type of parallel beam geometry has been widely used in single‐cell computational models . The plane source was put close to the cell surface at a distance to cell surface is 35 µm.…”

Section: Methodsmentioning

confidence: 99%

Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation

Liu

Zhao

et al. 2019

Medical Physics

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Purpose: The radiosensitization properties of gold nanoparticles (GNPs) are investigated using a simple Geant4 cell model considering a realistic cell geometry and a clustering algorithm to characterize the number of DNA double-strand breaks (DSBs). Materials and methods: A mixed-physics approach is taken for accurate modeling of low-energy photon interactions in the different regions of the model using Geant4-DNA physics within the cell, and Livermore physics within gold. Density-based spatial clustering of applications with noise (DBSCAN), a clustering algorithm, is used to directly quantitate DNA DSBs after irradiation. The simulation was run using different sizes of GNPs, different distances of GNPs from the cell nucleus, and several combinations of these two conditions. Results: Four types of radiation were simulated in the work: 80-keV monoenergetic photons, 100-keV monoenergetic photons, a 250-kVp photon spectrum, and a 6-MV flattening filter free (FFF) photon spectrum. A variable enhancement in DSB yield, nucleus dose, and cell dose was observed when there are GNPs in the cell cytoplasm, and increases with larger GNPs and proximity to the nucleus. The distance of the GNPs from the nucleus has a large impact on the DSB yield and nucleus dose, but little to no effect on the cell dose. The cell dose enhancement factor of 80 keV photons varies from 1.037-1.125 at 0.2 µm for 30-100 nm GNPs to 1.040-1.127 at 4 lm. The DSB enhancement factor varies from 1.050 to 1.174 at 0.2 µm to a marginal effect of <1.01 at 4 lm. For 100 keV, the dose enhancement factor is from 1.142-1.470 at 0.2 µm to 1.106-1.371 at 4 lm. The DSB enhancement factor varies from 1.249-1.813 at 0.2 µm to almost no effect at 4 lm. For 250 kVp, the dose enhancement factor is from 1.117-1.393 at 0.2 lm to 1.110-1.342 at 4 lm. The DSB enhancement factor varies from 1.183-1.600 at 0.2 lm to a marginal effect of~1.03 at 4 lm. A 6-MV FFF shows a dose enhancement factor of 1.061-1.103 at 0.2 lm and 1.053-1.107 at 4 lm. The DSB yield varies from 1.070-1.143 at 0.2 lm to a marginal effect at 4 lm. Conclusion: The stark difference in behavior for DSB yield when compared to cell dose highlights the importance of evaluating more complex radiobiological quantities rather than dose alone when evaluating the radiosensitization properties from metallic nanomaterials. The nucleus dose showed similar characteristics to the DSB yield demonstrating the ability of the method to predict DNA damage and its relationship with nuclear dose. The proposed method provides a way to explore the radiobiological mechanisms of radiation-induced DNA damages, and it aids to evaluate the physical radiosensitization properties of GNP-aided radiotherapy, which can be easily combined with radiochemical DSB quantitation in order to better understand the intricate DNA damage induction mechanisms that are involved in GNP-aided radiotherapy.

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“…It is well known that results for DERs are highly dependent on the simulation setup [29,30,31] and it was clearly stated in [26] that the shown DERs are valid only for the particular exposure scenario that was used for the simulations. As it has come to our attention that the results reported in [26,27] are prone to be misinterpreted at representing 'the' DERs of GNPs under diagnostic X-ray irradiation, this paper shows how much different the DERs would be for a GNP irradiated with an extended photon field.…”

Section: Introductionmentioning

confidence: 99%

Intercomparison of Monte Carlo calculated dose enhancement ratios for gold nanoparticles irradiated by X-rays: Assessing the uncertainty and correct methodology for extended beams

Rabus

Villagrasa

et al. 2021

Physica Medica

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Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in the order of several tens of micrometers from the GNP surface. As it has come to our attention that the figures in our paper have given rise to misinterpretation as showing 'the' DERs of GNPs under diagnostic X-ray irradiation, this article presents estimates of the DERs that would have been obtained with realistic radiation field extensions and presence of secondary particle equilibrium (SPE). These DER values are much smaller than those for a narrow-beam irradiation shown in our paper, and significant dose enhancement is only found within a few hundred nanometers around the GNP. The approach used to obtain these estimates required the development of a methodology to identify and, where possible, correct results from simulations whose implementation deviated from the initial exercise definition. Based on this methodology, literature on Monte Carlo simulated DERs has been critically assessed.

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The Dichotomous Nature of Dose Enhancement By Gold Nanoparticle Aggregates in Radiotherapy

Abstract: The peripheral dose enhancement may have less importance than the hotspots, which can have greater contribution to cell kill via radical creation. Hence, aggregate formation may be beneficial in nanoparticle-aided radiotherapy.

Cited by 12 publications

References 30 publications

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation

Intercomparison of Monte Carlo calculated dose enhancement ratios for gold nanoparticles irradiated by X-rays: Assessing the uncertainty and correct methodology for extended beams

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