Variations in Gold Nanoparticle Size on DNA Damage: A Monte Carlo Study Based on a Multiple-Particle Model Using Electron Beams

Round 1

Reviewer 1 Report

 

In this study, the Monte Carlo simulation using the Geant4-DNA code was used to investigate the effects of multiple GNPs on DNA damage when exposed to electron beams with energies of 50 keV, 100 keV, 150 keV, and 200 keV. The paper is well organized, but there are some comments should be considered:  

1-  While the study provides useful insights into the effects of gold nanoparticles on DNA damage under irradiation, there are a few potential issues that should be taken into consideration.

(a)   Firstly, the simulations were conducted under idealized conditions, which may not reflect the complexities and variations that could occur in real-world settings. For example, the simulations did not take into account the effects of biological tissues, which could impact the interactions between the nanoparticles and the incident electrons.

(b)   Secondly, the study used a simplified model of DNA, which may not fully represent the complex structure and dynamics of real DNA. This could limit the accuracy and relevance of the results obtained from the simulations.

(c)   Finally, the study did not provide experimental validation of the simulation results, which could raise questions about the reliability and reproducibility of the findings. While simulations can provide valuable insights, experimental validation is crucial to confirm and extend the results obtained from simulations.

 

2-Comparison table should be added. The proposed method with other related works should be compared.

3- Figure 1 (a) and (b) and Fig 3 (a), (b) and (c) parts should be emphasized in the depicted figures.

4-The legend should be written in Fig.5, like Fig 4.

5-Here are some grammar and language errors that can be found in the given study:

1.  "However, there was no change in the double- to single-strand break ratio despite the increase in DNA damage." This sentence is a bit confusing and could benefit from rephrasing.

2.  "cancer therapy" should be "cancer treatment"

3.  "electron beam" should be "electron beams"

4.  "accommodation" should be "combination"

5.  "radiosensitizers have been effective" should be "Radiosensitizers have been shown to be effective"

6.  "cancer cells [6-8]." has a space before the period

7.  "Good" should be lowercase

8.  "low toxicity biologically" should be "low biological toxicity"

9.  "EPR effect" should be "enhanced permeability and retention effect"

10.  "low permeability to the normal vasculature system" should be "low permeability to normal vasculature"

11.   "recoiled" should be "recoiling"

Author Response

Authors’ Responses

 

Authors: We would like to thank the Reviewer for their insightful comments regarding our manuscript. Our responses are marked in blue fonts while the corrections are marked in red fonts in the revised manuscript.

 

Reviewer 1

In this study, the Monte Carlo simulation using the Geant4-DNA code was used to investigate the effects of multiple GNPs on DNA damage when exposed to electron beams with energies of 50 keV, 100 keV, 150 keV, and 200 keV. The paper is well organized, but there are some comments should be considered: 

 

1- While the study provides useful insights into the effects of gold nanoparticles on DNA damage under irradiation, there are a few potential issues that should be taken into consideration.

 

(a)   Firstly, the simulations were conducted under idealized conditions, which may not reflect the complexities and variations that could occur in real-world settings. For example, the simulations did not take into account the effects of biological tissues, which could impact the interactions between the nanoparticles and the incident electrons.

 

Authors: We are grateful for your insightful comment. Our group has been at the forefront of publishing Monte Carlo simulation papers on single-gold nanoparticle nanodosimetry with DNA (e.g. Chow et al Phys Med Biol 2012;47:3323 and Leung et al Med Phys 2011;38:624), continually refining both simulation geometry and DNA model details over the years. In this work, we have, for the first time, considered a multiple-gold nanoparticle model to assess DNA damage. Moving forward, we plan to focus on building a more realistic simulation model based on biological tissues to account for the complex interactions between nanoparticles and incident electrons in cancer cells. We added the following statements in Section 4.4:

 

Ongoing research aims to construct a more realistic simulation model based on biological tissues that can account for the interactions between nanoparticles and incident electrons, thereby reflecting the complexities of a cancer cell in real-world settings.

 

(b)   Secondly, the study used a simplified model of DNA, which may not fully represent the complex structure and dynamics of real DNA. This could limit the accuracy and relevance of the results obtained from the simulations.

 

Authors: In our Monte Carlo simulation studies focused on DNA damage, we continually update the DNA model to improve accuracy. Initially, we investigated DNA dosimetry and damage by assuming the DNA was a homogeneous volume-of-interest (Chun et al AIM Bioeng 2016;3:352). Two years ago, we updated the model (Jabeen et al Nanomaterials 2021;11:1751 and Ngoc et al App Sci 2021;11:10856) and have now further improved it in this work. Our commitment to accuracy means that we will continue to refine the model in future studies. We added the following statement in Section 4.4:

 

Moreover, as soon as a more realistic DNA model becomes available, it will be incorporated into the simulation.

 

(c)   Finally, the study did not provide experimental validation of the simulation results, which could raise questions about the reliability and reproducibility of the findings. While simulations can provide valuable insights, experimental validation is crucial to confirm and extend the results obtained from simulations.

 

Authors: Experimental validation of Monte Carlo simulation models for nanodosimetry is challenging due to the requirement for measuring equipment at the nanometer scale, which is difficult to fabricate and manipulate. Consequently, there is limited verification data available. In our research, we prioritize analyzing the trend of the dependence of irradiation variables on DNA damage over predicting absolute dosimetric results. This approach has proven helpful in designing heavy-atom nano-radiosensitizers for nanoparticle-enhanced radiotherapy in our field of study.

 

2-Comparison table should be added. The proposed method with other related works should be compared.

 

Authors: This is the first time a multiple-gold nanoparticle model is developed to access the DNA damage according to our specific simulation geometry. There is no other similar study published before for comparison.

 

3- Figure 1 (a) and (b) and Fig 3 (a), (b) and (c) parts should be emphasized in the depicted figures.

 

Authors: Corrected.

 

4-The legend should be written in Fig.5, like Fig 4.

 

Authors: Corrected.

 

5-Here are some grammar and language errors that can be found in the given study:

 

1. "However, there was no change in the double- to single-strand break ratio despite the increase in DNA damage." This sentence is a bit confusing and could benefit from rephrasing.

 

Authors: We rephrased the sentences as follows:

 

Although DNA damage increased, the proportion of double-strand breaks remained unchanged in relation to the total number of strand breaks.

 

2. "cancer therapy" should be "cancer treatment"

 

Authors: Done.

 

3. "electron beam" should be "electron beams"

 

Authors: Done.

 

4. "accommodation" should be "combination"

 

Authors: Done.

 

5. "radiosensitizers have been effective" should be "Radiosensitizers have been shown to be effective"

 

Authors: Done.

 

6. "cancer cells [6-8]." has a space before the period

 

Authors: Corrected.

 

7. "Good" should be lowercase

 

Authors: Corrected.

 

8. "low toxicity biologically" should be "low biological toxicity"

 

Authors: Corrected.

 

9. "EPR effect" should be "enhanced permeability and retention effect"

 

Authors: Done.

 

10. "low permeability to the normal vasculature system" should be "low permeability to normal vasculature"

 

Authors: Done.

 

11. "recoiled" should be "recoiling"

 

Authors: Done.

Author Response File: Author Response.pdf

Reviewer 2 Report

Please defined nanoparticles, and why could be useful to use these types of particles, maybe the mechanism

In clinical practice in which types of cancers you think that could be use in the future ?

Author Response

Authors’ Responses

 

Authors: We would like to thank the Reviewer for their insightful comments regarding our manuscript. Our responses are marked in blue fonts while the corrections are marked in red fonts in the revised manuscript.

 

Reviewer 2

Please defined nanoparticles, and why could be useful to use these types of particles, maybe the mechanism

 

Authors: We added the following paragraph in the Introduction Section:

 

A nanoparticle is a small particle with at least one dimension measuring between 1 to 100 nanometers [15]. These particles can be made of various materials, such as metals, ceramics, or polymers. Nanoparticles have unique properties due to their size, including a high surface-to-volume ratio, increased reactivity, and unique optical and magnetic properties [9]. In radiotherapy, nanoparticles are used to enhance the effectiveness of radiation treatment. When a nanoparticle is irradiated with radiation, it can interact with the radiation and cause the release of secondary electrons, which can cause more damage to cancer cells [16, 24]. Additionally, nanoparticles can be designed to preferentially accumulate in cancer cells due to the enhanced permeability and retention effect, resulting in a higher concentration of the particles in the tumor. This allows for more targeted and precise de-livery of radiation to cancer cells, sparing healthy surrounding tissues [6, 8].

 

In clinical practice in which types of cancers you think that could be use in the future?

 

Authors: We added the following paragraph in the Introduction Section with additional references:

 

Nanoparticle radiation therapy has shown promise for a variety of cancer types. For example, heavy-atom nanoparticles such as GNPs can be used to enhance the effectiveness of radiation therapy for prostate cancer by improving the distribution of radiation within the tumor and providing dose enhancement [25]. In addition, nanoparticles have been used to deliver radiation therapy directly to lung tumors, improving the effectiveness of treatment and minimizing damage to healthy surrounding tissues [26]. The use of GNPs as a radiosensitizer has been shown to be effective in enhancing the dose for skin lesions when using orthovoltage beams in skin therapy [27].

 

25. Martelli S, Chow JCL. Dose enhancement for the flattening-filter-free and flattening-filter photon beams in nanoparticle-enhanced radiotherapy: A Monte Carlo phantom study. Nanomaterials 2020, 10, 637.
26. Carrasco-Esteban E, Domínguez-Rullán JA, Barrionuevo-Castillo P, Pelari-Mici L, Leaman O, Sastre-Gallego S, López-Campos F. Current role of nanoparticles in the treatment of lung cancer. Journal of Clinical and Translational Research. 2021 Apr 4;7(2):140.
27. Sadiq A, Chow JCL. Evaluation of Dosimetric Effect of Bone Scatter on Nanoparticle-Enhanced Orthovoltage Radiotherapy: A Monte Carlo Phantom Study. Nanomaterials 2022, 12, 2991.

Author Response File: Author Response.pdf