Graphene Oxide (GO) for the Treatment of Bone Cancer: A Systematic Review and Bibliometric Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Barba-Rosado et al. have aimed to make a systematic review and bibliometric analysis on the use of graphene oxide for treatment of bone cancer. Although the topic is of interest, the bibliometric analysis is not systematically/completely made and there are problems with reference citations in tables and text. Also, the reference citations are allowed to run with continuous numbers from text to table and back to text, which is not a proper presentation as the tables may be relocated in positioning during printing. Therefore, I suggest a major revision for thorough improvement in bibliometric section, rearrangement of messy reference citations and comparative discussion under each topic as shown below:

1.        Some bibliometric information provided in lines 28-33 in the abstract and lines 706-712 in the conclusion are not mentioned anywhere inside the manuscript.

2.        The bibliometric analysis should contain a year-wise growth of publication plot, country-wise distribution in world map, year-wise number of citations plot and journal impact factor-based publication plot. Instead only a couple of sentences are given in abstract and conclusion. I suggest that the topic “2. Methodology” should be replaced with “2. Bibliometric analysis” containing already included information along with a discussion on the year-wise publication growth plot, the country-wise distribution, year-wise number of citations and journal impact factor-based publication.

3.        The keywords “bone cancer” and “bibliometric analysis” should be included.

4.        In Figure 3, include an explanatory legend to indicate what that radiation / wifi symbol denote.

5.        Section 3.1.4, let the topic be expanded to be specific as to what action mechanisms.

6.        As much as the discussion made for photodynamic and photothermal therapy, the discussions on in vitro studies and in vivo studies in section 3.1.5.1 and 3.1.5.2 respectively are not elaborate.

7.        It is confusing as to why there are references [90, 91, 92] cited in section 3.1.5.1 for in vitro study, but the in vitro studies in Table 1 correspond to [96, 97, 98]. The same for in vivo study in section 3.1.5.2 and that in Table 1. The references in Tables should be discussed in respective sections.

8.        Likewise, the references discussed under photodynamic and photothermal therapies should correspond to that tabulated in Table 2 and Table 3 respectively. The references in Tables should be discussed in respective sections.

9.        Under each section a final paragraph should outline the comparative account of the discussion made under that topic.

10.     Future perspectives should be presented as one paragraph.

11.     Conclusions should be reduced and made into one paragraph.

12.     In references, doi is provided for some and not for some.

13.     In the reference citation in text, some are provided in (author, year) format.

14.     All the abbreviations used in Tables 1-3 should be given in full form in the respective table’s footer.

Comments on the Quality of English Language

Moderate editing of English language required

Author Response

Dear Reviewer,

We want to submit our corrected version of the paper entitled "Graphene oxide (GO) for treating bone cancer: A systematic review and bibliometric analysis" by Lemy Vanessa Barba-Rosado, Domingo Cesar Carrascal-Hernández, Daniel Insuasty, and Carlos David Grande-Tovar, who agreed with all the corrections. The corrections are presented below point by point in red for easy comprehension.

Reviewer 1

Barba-Rosado et al. have aimed to make a systematic review and bibliometric analysis on the use of graphene oxide for treatment of bone cancer. Although the topic is of interest, the bibliometric analysis is not systematically/completely made, and there are problems with reference citations in tables and text.

R// We appreciate the comment. However, the bibliometric analysis was included as supporting information to avoid a very extensive document. That was indicated in the final section regarding supporting information in the manuscript but also mentioned in each section (abstract, introduction, and conclusions). Between lines 870-880, the explanation was initially given.

Also, the reference citations are allowed to run with continuous numbers from text to table and back to text, which is not a proper presentation as the tables may be relocated in positioning during printing.

R// We agreed with the reviewer. Some of the references from the tables were discussed in the text. However, we also discussed some other references for comparison and other purposes. 

Therefore, I suggest a major revision for thorough improvement in the bibliometric section, rearrangement of messy reference citations, and comparative discussion under each topic as shown below:

1. Some bibliometric information provided in lines 28-33 in the abstract and lines 706-712 in the conclusion are not mentioned anywhere inside the manuscript.

R// We appreciate the comment. However, the document's extension included the bibliometric analysis as supporting information. That was indicated in the final section regarding supporting information but also mentioned in each section (abstract, introduction, and conclusions). Between lines 870-880, the explanation was initially given.

2. The bibliometric analysis should contain a year-wise growth of publication plot, country-wise distribution in world map, year-wise number of citations plot and journal impact factor-based publication plot. Instead only a couple of sentences are given in abstract and conclusion. I suggest that the topic “2. Methodology” should be replaced with “2. Bibliometric analysis” containing already included information along with a discussion on the year-wise publication growth plot, the country-wise distribution, year-wise number of citations and journal impact factor-based publication.

R// We tried to follow the reviewer’s comment. However, it is not clear since all the requirements were included in the supporting section as Figures S1-S4 and Tables 1-2. We have a year-wise growth publication plot, country-wise distribution map, keywords map, and tables with all the most cited papers and most publishing journals on the topics with their Citescore and journal impact factor information. That was indicated in the final section regarding supporting information, and the sections were mentioned (abstract, introduction, and conclusions). Between lines 870-880, the explanation was initially given. The decision to remove the information from the supporting section is because the journal is not focusing on bibliometric analysis; since ours is just used to support the systematic review, we removed that section. However, it still delivers essential information about the perspective of the topic.

3. The keywords “bone cancer” and “bibliometric analysis” should be included.

R// We appreciate the reviewer’s suggestion. The suggested keywords were added.

4. In Figure 3, include an explanatory legend to indicate what that radiation/wifi symbol denotes.

R// We appreciate the reviewer´s suggestion. The suggested explanatory legend to indicate what that radiation symbol denotes is included in Figure 3.

5. Section 3.1.4, let the topic be expanded to be specific as to what action mechanisms.

R// We appreciate the reviewer´s suggestion. The section was expanded to explain the action mechanism.

6. As much as the discussion made for photodynamic and photothermal therapy, the discussions on in vitro studies and in vivo studies in sections 3.1.5.1 and 3.1.5.2, respectively, are not elaborate.

R// We appreciate the reviewer´s suggestion. In vitro and In vivo studies added more information and improved discussion.

7. It is confusing as to why there are references [90, 91, 92] cited in section 3.1.5.1 for in vitro study, but the in vitro studies in Table 1 correspond to [96, 97, 98]. The same for in vivo study in section 3.1.5.2 and that in Table 1. The references in Tables should be discussed in respective sections.

R// We appreciate the reviewer´s suggestion. In vitro and In vivo studies references cited in Table 1 hadn't been mentioned in the discussion. However, they have been already included in the corresponding section.

8. Likewise, the references discussed under photodynamic and photothermal therapies should correspond to that tabulated in Table 2 and Table 3 respectively. The references in Tables should be discussed in respective sections.

R// We appreciate the reviewer´s suggestion. The references tabulated in Table 2 and Table 3 for photodynamic and photothermal therapy were included in the discussion.

9. Under each section a final paragraph should outline the comparative account of the discussion made under that topic.

R// We appreciate the reviewer´s suggestion. A final paragraph that summarizes the comparative account of the discussion was added in each section.

10. Future perspectives should be presented as one paragraph.

R// We appreciate the reviewer´s suggestion. The future perspectives section was compacted into one paragraph.

11. Conclusions should be reduced and made into one paragraph.

R// We appreciate the reviewer´s suggestion. Conclusions were compacted into one paragraph.

12. In references, doi is provided for some and not for some.

R// We appreciate the reviewer´s suggestion. Now, each reference provides its doi, except for references 1, 8, 16, 26, and 29, which we could not find.

13. In the reference citation in text, some are provided in (author, year) format.

R// We appreciate the reviewer´s suggestion. The reference citation format was corrected.

14. All the abbreviations used in Tables 1-3 should be given in full form in the respective table’s footer.

R// We appreciate the reviewer´s suggestion. Abbreviations in complete form were added to the respective table’s footer in Tables 1-3.

Reviewer 2 Report

Comments and Suggestions for Authors

A) Summary of Key Results, Significance & Reliability of Conclusions:
Lemy Vanessa Barba-Rosado manuscript presents a thorough review analyzing the use of graphene oxide (GO) in treating osteosarcoma, highlighting its potential through various therapeutic approaches such as photodynamic therapy, photothermal therapy, and nanocarriers. The review includes a bibliometric analysis, demonstrating the high-impact nature of this field. The conclusions drawn emphasize the promising aspects of GO-based nanomaterials for bone cancer treatment and the advancements in phototherapy techniques.

On the overall, this will be a great addition to Nanomaterials readership, and certainly stimulate further works. Thus I recommend publication with minor corrections noted

B) Originality & Validity of the Approach:
The review offers a comprehensive overview of existing literature, showcasing the evolution and trends in GO-based therapies for osteosarcoma. It effectively emphasizes the potential synergy between photodynamic and photothermal therapies and the enhanced efficiency achieved through functionalization and biomolecule integration. However, a notable gap appears in the absence of discussion around the atomic understanding of protein adsorption and the biocompatibility of these materials.

C) Suggested Improvements:
While the review provides a strong foundation, it could benefit from an expanded exploration of the atomic-level understanding of protein adsorption onto GO and its derivatives (solvents J. Chem. Theory Comput. 2019, 15, 4, 2548–2560). Additionally, discussing the biocompatibility aspects would significantly enhance the manuscript's completeness. While it is true that not as much has been done on GO, however for graphene this was quite a prolific field and thus merits mention in future prespectives. Exploring these dimensions would further strengthen the understanding of these materials' interaction with biological systems, contributing to a more comprehensive review.

The manuscript presents a commendable effort in summarizing the use of GO-based nanomaterials for osteosarcoma treatment. However, addressing the lacuna in atomic-level understanding of protein adsorption and biocompatibility would significantly bolster the manuscript's comprehensiveness and contribute to a more holistic discussion in this field.

Author Response

Dear Reviewer,

We want to submit our corrected version of the paper entitled "Graphene oxide (GO) for treating bone cancer: A systematic review and bibliometric analysis" by Lemy Vanessa Barba-Rosado, Domingo Cesar Carrascal-Hernández, Daniel Insuasty, and Carlos David Grande-Tovar, who agreed with all the corrections. The corrections are presented below point by point in red for easy comprehension.

Reviewer 2

1. A) Summary of Key Results, Significance & Reliability of Conclusions:

Lemy Vanessa Barba-Rosado's manuscript presents a thorough review analyzing the use of graphene oxide (GO) in treating osteosarcoma, highlighting its potential through various therapeutic approaches such as photodynamic therapy, photothermal therapy, and nanocarriers. The review includes a bibliometric analysis, demonstrating the high-impact nature of this field. The conclusions drawn emphasize the promising aspects of GO-based nanomaterials for bone cancer treatment and the advancements in phototherapy techniques.

On the overall, this will be a great addition to Nanomaterials readership, and certainly stimulate further works. Thus I recommend publication with minor corrections noted

R// We appreciate the favorable comment of the reviewer.

1. B) Originality & Validity of the Approach:

The review offers a comprehensive overview of existing literature, showcasing the evolution and trends in GO-based therapies for osteosarcoma. It effectively emphasizes the potential synergy between photodynamic and photothermal therapies and the enhanced efficiency achieved through functionalization and biomolecule integration. However, a notable gap appears in the absence of discussion around the atomic understanding of protein adsorption and the biocompatibility of these materials.

R// We appreciate your suggestions. The atomic understanding of protein adsorption and the biocompatibility of nanomaterials in graphene oxide were developed. The section on nanocarriers goes into depth about the topic.

1. C) Suggested Improvements:

While the review provides a strong foundation, it could benefit from an expanded exploration of the atomic-level understanding of protein adsorption onto GO and its derivatives (solvents J. Chem. Theory Comput. 2019, 15, 4, 2548–2560). Additionally, discussing the biocompatibility aspects would significantly enhance the manuscript's completeness. While it is true that not as much has been done on GO, however for graphene this was quite a prolific field and thus merits mention in future prespectives. Exploring these dimensions would further strengthen the understanding of these materials' interaction with biological systems, contributing to a more comprehensive review.

R// We appreciate your suggestions. The atomic understanding of protein adsorption and the biocompatibility of nanomaterials in graphene oxide were developed. The section on nanocarriers goes into depth about the topic.

The manuscript presents a commendable effort in summarizing the use of GO-based nanomaterials for osteosarcoma treatment. However, addressing the lacuna in atomic-level understanding of protein adsorption and biocompatibility would significantly bolster the manuscript's comprehensiveness and contribute to a more holistic discussion in this field.

R// We appreciate your suggestions. The atomic understanding of protein adsorption and the biocompatibility of nanomaterials in graphene oxide were developed. The section on nanocarriers goes into depth about the topic.

• We sincerely appreciate your comments and suggestions. As an essential update, we would like to inform you that, following the editor’s initial recommendation, we have removed Image 4 from the review. The information on the use of GO in anticancer applications is already detailed in the section, and this does not affect the quality of the manuscript. Consequently, it was not necessary to apply for a copyright license. Thank you for your understanding.
• We also want to highlight that the name of Table 1 was updated for a better comprehension of the content, and Figure 1 was corrected according to the corrections made in the manuscript.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have satisfactorily addressed all the comments raised by reviewers and substantially improved the overall quality of the article. Therefore I recommend accepting this article for publication in Nanomaterials.

Comments on the Quality of English Language

Minor editing of English language required