Physical Radiation Enhancement Effects Around Clinically Relevant Clusters of Nanoagents in Biological Systems

Villagomez‐Bernabe, Balder; Currell, Frederick

doi:10.1038/s41598-019-44482-y

Cited by 22 publications

(26 citation statements)

References 28 publications

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“…To illustrate this, we pick a specific application domain—the radiosensitization due to enhanced dose deposition around nanoparticles. While this application domain has been chosen because it is amenable to quantified calculation with the relevant computational machinery being at hand, this finding illustrates the importance for any causal effect expected to be local to the nanoparticles. In fact, the dose enhancement roughly falls off with the second inverse power of distance from the nanoparticle, that is, d −2 where d is the distance between the nanoparticle and the site of effect.…”

Section: Resultsmentioning

confidence: 99%

“…Dose Deposition Simulation : The dose enhancement due to the Au‐NPs was calculated using a multiscale Monte Carlo method . Using Topas, a clinical linac spectrum, after transport through 3 cm of soft tissue, was further transported through a single nanoparticle (including its coating) with the outgoing phase space of all particles interacting with the nanoparticle or its coating being captured.…”

Section: Methodsmentioning

confidence: 99%

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Nuclear Uptake of Gold Nanoparticles Deduced Using Dual‐Angle X‐Ray Fluorescence Mapping

McCulloch

Bennie

Coulter

et al. 2019

Part & Part Syst Charact

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Studies into the cell nucleus' incorporation of gold nanoparticles (AuNPs) are often limited by ambiguities arising from conventional imaging techniques. Indeed, it is suggested that to date there is no unambiguous imaging evidence for such uptake in whole cells, particularly at the single nanoparticle level. This shortcoming in understanding exists despite the nucleus being the most important subcellular compartment in eukaryotes and gold being the most commonly used metal nanoparticle in medical applications. Here, dual‐angle X‐ray flouresence is used to show individually resolved nanoparticles within the cell nucleus, finding them to be well separated and 79% of the intranuclear population to be monodispersed. These findings have important implications for nanomedicine, illustrated here through a specific exemplar of the predicted enhancement of radiation effects arising from the observed AuNPs, finding intranuclear dose enhancements spanning nearly five orders of magnitude.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Nuclear Uptake of Gold Nanoparticles Deduced Using Dual‐Angle X‐Ray Fluorescence Mapping

McCulloch

Bennie

Coulter

et al. 2019

Part & Part Syst Charact

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“…One of the major limitations in current RT is that the dose cannot be further increased due to normal tissue toxicity. One of the ways to increase the local dose to the tumour is through the introduction of high Z materials such as GNPs [12][13][14][15][16][17][18][19][20][21] . Hence, one of the goals of this study was to evaluate the GNP uptake and resulting damage due to radiation in normal cells such as FBs compared to cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Gold nanoparticle mediated radiation response among key cell components of the tumour microenvironment for the advancement of cancer nanotechnology

Bromma

Cicon

Beckham

et al. 2020

Sci Rep

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one of the major issues in cancer radiotherapy (Rt) is normal tissue toxicity. introduction of radiosensitizers like gold nanoparticles (Gnps) into cancer cells to enhance the local Rt dose has been tested successfully. However, it is not known how Gnps interact with other stromal cells such as normal fibroblasts (FBs) and cancer associated fibroblasts (CAFs) within the tumour microenvironment. It is known that FBs turn into CAFs to promote tumour growth. Hence, we used FBs and CAFs along with HeLa (our cancer cell line) to evaluate the differences in GNP uptake and resulting radiation induced damage to elucidate the GNP-mediated therapeutic effect in RT. The CAFs had the largest uptake of the GNPs per cell, with on average 265% relative to HeLa while FBs had only 7.55% the uptake of HeLa and 2.87% the uptake of CAFs. This translated to increases in 53BP1-related DNA damage foci in CAFs (13.5%) and HeLa (9.8%) compared to FBs (8.8%) with RT treatment. This difference in DNA damage due to selective targeting of cancer associated cells over normal cells may allow GNPs to be an effective tool in future cancer RT to battle normal tissue toxicity while improving local Rt dose to the tumour. Cancer is a family of diseases arising from dysregulation of the expression of multiple genes, leading to abnormal cell proliferation and cell death. As a result, there is significant morbidity in patients if left untreated 1. Before the age of 75, about 1 in 6 people will develop cancer while 1 in 9 will die from it 2. Aside from surgery, one of the main modalities employed in the treatment of cancer is radiotherapy (RT). RT aims to deliver high doses of ionizing radiation to cancerous tissue, inducing death from damage to important structures such as the DNA or mitochondria 3. Despite being used in 50% of all patients diagnosed with cancer, one of the major issues in current RT modalities is the normal tissue toxicity in radiosensitive tissue localized closely with the cancer 4,5. Furthermore, there are many radiobiological hurdles to overcome, such as the influence of cancer stem cells, tumour heterogeneity, tumour hypoxia, metabolic pathways, and other complications, that will increase the radioresistance of the tumour cells 6-8. While the introduction of targeting methods such as volumetric modulated arc therapy (VMAT) and image guided radiotherapy (IGRT) has improved the efficacy of RT, there is a limit of improvement when it comes to the use of RT as a singular treatment modality 9. In an effort towards reducing the normal tissue toxicity while increasing the damage to the tumour, radiosensitizers have been introduced 10. Radiosensitizers work via various pathways, such as targeting of the radioresistant hypoxic cells in tumours, or through production of reaction oxygen species (ROS) 10,11. The introduction of high atomic number materials into tumour tissue has been explored as a promising approach to enhance the local radiation dose 12-17 .

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“…Historically there have been broadly two approaches to relate physical radiation transport processes to biological outcome, target theory [3,18] and energy deposition [15][16][17]. Although it is an open question and one requiring further research, we argue that a target theory-based approach is more appropriate.…”

Section: Discussionmentioning

confidence: 93%

“…Only ionisation events were used for this process, rather than energy deposition events as was done previously [5]. Although energy deposition approaches have been very successful in predicting biological outcomes in other nanoscale radiobiology contexts [15][16][17], we argue in the discussion section that more of a targettheory inspired approach [3,18] is appropriate, although we admit this is an open question and one worthy of further investigation. However, none of the conclusions reached regarding the role of RNA tertiary/quaternary structure depend on the choice between energy deposition or target theory approaches.…”

Section: Fast Ion Irradiation Of the Sars-cov Virionmentioning

confidence: 99%

Fast Ion Beam Inactivation of Viruses, Where Radiation Track Structure Meets RNA Structural Biology

Villagomez‐Bernabe

Chan

Coulter

et al. 2020

Preprint

Self Cite

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Here we show an interplay between the structures present in ionization tracks and nucleocapsid RNA structural biology, using fast ion beam inactivation of the severe acute respiratory syndrome coronavirus (SARS-CoV) virion as an example. This interplay is one of the key factors in predicting dose-inactivation curves for high energy ion beam inactivation of virions. We also investigate the adaptation of well-established cross-section data derived from radiation interactions with water to the interactions involving the components of a virion, going beyond the density-scaling approximation developed previously. We conclude that solving one of the grand challenges of structural biology - the determination of RNA tertiary/quaternary structure structure - is intimately linked to predicting ion-beam inactivation of viruses and that the two problems can be mutually informative. Indeed, our simulations show that fast ion beams have a key role to play in elucidating RNA tertiary/quaternary structure.

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Physical Radiation Enhancement Effects Around Clinically Relevant Clusters of Nanoagents in Biological Systems

Cited by 22 publications

References 28 publications

Nuclear Uptake of Gold Nanoparticles Deduced Using Dual‐Angle X‐Ray Fluorescence Mapping

Nuclear Uptake of Gold Nanoparticles Deduced Using Dual‐Angle X‐Ray Fluorescence Mapping

Gold nanoparticle mediated radiation response among key cell components of the tumour microenvironment for the advancement of cancer nanotechnology

Fast Ion Beam Inactivation of Viruses, Where Radiation Track Structure Meets RNA Structural Biology

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