Nanomedicine as a Promising Treatment Approach for Obesity

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Obesity is a chronic disease linked to serious health complications, including diabetes, cardiovascular disease, and cancer. Traditional treatments—such as lifestyle changes, medications, and surgery—often have limited effectiveness and can cause side effects. This review explores the emerging role of nanomedicine as a novel therapeutic strategy for obesity. Nanotechnology-based approaches offer targeted delivery and improved efficacy, addressing some of the shortcomings of conventional therapies. The article discusses various nanomedicine strategies, including targeting white adipose tissue, stimulating the browning of fat, and using photothermal and magnetic hyperthermia therapies. It also covers gene nanotherapy and addresses concerns about the potential toxicity of nanomedicine. Overall, the review highlights nanomedicine’s promise in obesity management while acknowledging the need for further research to ensure safety and effectiveness.

I have few comments to improve even further the text:

Title & Abstract
The title accurately reflects the focus of the manuscript, clearly indicating that the article reviews nanomedicine as a novel approach for obesity treatment. The abstract succinctly summarizes the background, the limitations of traditional therapies, and the scope of the review, including key nanotechnological strategies and their potential. However, the abstract could be improved by briefly mentioning the main types of nanomedicine discussed (e.g., nanoparticles, photothermal therapy) and by including a sentence on key findings or conclusions from the review.

Review Novelty
The introduction provides a comprehensive overview of obesity, including definitions, epidemiology, pathophysiology, complications, and economic burden. The background is thorough and well-referenced, allowing readers to understand the significance and context of the research. However, the review could better articulate the precise scientific or clinical gaps in nanomedicine research for obesity (e.g., lack of translational studies, safety concerns, or challenges in targeting specific tissues). While the need for new therapies is clear, a sharper focus on what is lacking in current research would strengthen the rationale for the review.
The review covers emerging nanomedicine strategies for obesity, such as targeting white adipose tissue, stimulating browning, and employing photothermal/magnetic hyperthermia. These areas are indeed novel and represent a meaningful contribution by synthesizing current knowledge and highlighting future directions.  The discussion is grounded in current literature, and the mechanisms described are plausible based on cited studies. However, more critical analysis of the limitations and translational challenges would strengthen the manuscript. The authors should ensure that the references cited in this manuscript are appropriate and relevant. For example, 
"A recent systematic review in 2023 by Nagi et al, ... overall healthcare costs (25) (Lines 147-149)" It should be cited as 2024.
Ref 25. Nagi MA, Ahmed H, Rezq MAA, Sangroongruangsri S, Chaikledkaew U, Almalki Z, et al. Economic costs of obesity: a systematic review. Int J Obes. 2024 Jan;48(1):33–43. 
"In a mouse model, Xuea et al examined" (Line 275). It should be amended as Xue et al.

Conclusion
The conclusions are consistent with the review’s content, emphasizing the promise of nanomedicine while acknowledging potential toxicity and translational hurdles. However, the conclusion could be strengthened by outlining specific recommendations for future research and clinical trials.  A more actionable conclusion—highlighting specific research priorities, clinical trial needs, or regulatory considerations—would provide greater value for readers and researchers. A brief summary of the most promising nanomedicine modalities would be helpful.

Figures & Tables
Figures are clear and relevant, effectively illustrating key concepts. I noted that Figures 2-4 were all created with BioRender.com. In accordance with BioRender’s requirements for copyrighted images, authors will need to provide "Confirmation of Publication and Licensing Rights" to prove that they are authorized to use the Biorender images. 

Additional Considerations
References Relevance
The references cited in the introduction and throughout the text include both foundational and recent studies. There is a balanced mix, with a notable proportion of references from the last 5–10 years, including a 2023 systematic review and recent cost analyses. This suggests the review is up-to-date, with approximately 60–70% of references being from the last decade, and the remainder foundational or landmark studies. The authors should ensure that the references cited in this manuscript are appropriate and relevant. For example, "A recent systematic review in 2023 by Nagi et al, ... overall healthcare costs (25) (Lines 147-149)" It should be cited as 2024.
Validate all references to ensure they correspond to the stated claims.

Reference Style
Reference formatting appears consistent, but a full review of the reference list is needed to confirm adherence to journal guidelines.

Author Response

Nanomedicine as a Promising Treatment Approach for Obesity

05/07/2025

We sincerely thank the reviewers for their constructive feedback, which has helped us improve the quality and clarity of our manuscript. We have carefully addressed each comment point by point, as detailed below. 

All changes made in response to the reviewers’ suggestions have been clearly highlighted in yellow in the revised manuscript for ease of reference.

  

Reviewer 1

Comments and Suggestions for Authors

Obesity is a chronic disease linked to serious health complications, including diabetes, cardiovascular disease, and cancer. Traditional treatments—such as lifestyle changes, medications, and surgery—often have limited effectiveness and can cause side effects. This review explores the emerging role of nanomedicine as a novel therapeutic strategy for obesity. Nanotechnology-based approaches offer targeted delivery and improved efficacy, addressing some of the shortcomings of conventional therapies. The article discusses various nanomedicine strategies, including targeting white adipose tissue, stimulating the browning of fat, and using photothermal and magnetic hyperthermia therapies. It also covers gene nanotherapy and addresses concerns about the potential toxicity of nanomedicine. Overall, the review highlights nanomedicine’s promise in obesity management while acknowledging the need for further research to ensure safety and effectiveness.

I have few comments to improve even further the text:

1-Title & Abstract
The title accurately reflects the focus of the manuscript, clearly indicating that the article reviews nanomedicine as a novel approach for obesity treatment. The abstract succinctly summarizes the background, the limitations of traditional therapies, and the scope of the review, including key nanotechnological strategies and their potential. However, the abstract could be improved by briefly mentioning the main types of nanomedicine discussed (e.g., nanoparticles, photothermal therapy) and by including a sentence on key findings or conclusions from the review.

Reply: We appreciate the reviewer’s positive feedback and constructive suggestions. In response, we have revised the abstract to briefly mention the main types of nanomedicine discussed in the review. We  have also included a concluding sentence summarizing the key insights.

 

2-Review Novelty
The introduction provides a comprehensive overview of obesity, including definitions, epidemiology, pathophysiology, complications, and economic burden. The background is thorough and well-referenced, allowing readers to understand the significance and context of the research. However, the review could better articulate the precise scientific or clinical gaps in nanomedicine research for obesity (e.g., lack of translational studies, safety concerns, or challenges in targeting specific tissues). While the need for new therapies is clear, a sharper focus on what is lacking in current research would strengthen the rationale for the review.

The review covers emerging nanomedicine strategies for obesity, such as targeting white adipose tissue, stimulating browning, and employing photothermal/magnetic hyperthermia. These areas are indeed novel and represent a meaningful contribution by synthesizing current knowledge and highlighting future directions.  The discussion is grounded in current literature, and the mechanisms described are plausible based on cited studies. However, more critical analysis of the limitations and translational challenges would strengthen the manuscript.

Reply: In response to the reviewer’s comments, we have added a brief paragraph on page 5, line 216, to highlight key weaknesses in current nanomedicine research for obesity. Additionally, we have included a new subsection (Section 2.3: “Challenges Associated with Nanomedicines That Restrict Their Translation into Clinical Use”, page 15), which provides a more detailed discussion of the technological, clinical, and regulatory limitations. Furthermore, we have added remarks on the limitations of nanotherapeutic approaches in the Conclusion (page 16) to further strengthen the critical analysis of translational challenges.

3-The authors should ensure that the references cited in this manuscript are appropriate and relevant. For example, 
"A recent systematic review in 2023 by Nagi et al, ... overall healthcare costs (25) (Lines 147-149)" It should be cited as 2024.
Ref 25. Nagi MA, Ahmed H, Rezq MAA, Sangroongruangsri S, Chaikledkaew U, Almalki Z, et al. Economic costs of obesity: a systematic review. Int J Obes. 2024 Jan;48(1):33–43. 
"In a mouse model, Xuea et al examined" (Line 275). It should be amended as Xue et al.

Reply: The correction has been implemented as suggested.

4-Conclusion
The conclusions are consistent with the review’s content, emphasizing the promise of nanomedicine while acknowledging potential toxicity and translational hurdles. However, the conclusion could be strengthened by outlining specific recommendations for future research and clinical trials.  A more actionable conclusion—highlighting specific research priorities, clinical trial needs, or regulatory considerations—would provide greater value for readers and researchers. A brief summary of the most promising nanomedicine modalities would be helpful.

Reply: The conclusion has been revised in accordance with the reviewer’s recommendations.

5-Figures & Tables
Figures are clear and relevant, effectively illustrating key concepts. I noted that Figures 2-4 were all created with BioRender.com. In accordance with BioRender’s requirements for copyrighted images, authors will need to provide "Confirmation of Publication and Licensing Rights" to prove that they are authorized to use the Biorender images. 

Reply: We have an active BioRender membership and can provide the receipt to the journal editor upon request.

 

6-Additional Considerations
References Relevance
The references cited in the introduction and throughout the text include both foundational and recent studies. There is a balanced mix, with a notable proportion of references from the last 5–10 years, including a 2023 systematic review and recent cost analyses. This suggests the review is up-to-date, with approximately 60–70% of references being from the last decade, and the remainder foundational or landmark studies. The authors should ensure that the references cited in this manuscript are appropriate and relevant. For example, "A recent systematic review in 2023 by Nagi et al, ... overall healthcare costs (25) (Lines 147-149)" It should be cited as 2024.
Validate all references to ensure they correspond to the stated claims.

Reply: The correction has been made

7-Reference Style
Reference formatting appears consistent, but a full review of the reference list is needed to confirm adherence to journal guidelines.

Reply: The reference style has been revised to comply with the journal's guidelines

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Major

1. As this is a review article, the number of references is clearly insufficient. Typically, review articles are expected to include around 100 to 150 references to comprehensively cover the relevant literature.
2. Table 1 summarizes the description and disadvantages of each type of treatment. I would like to suggest that the advantages of each treatment type should also be included in the table for a more balanced and comprehensive comparison.
3. This review article aims to explore the role of nanomedicine and its potential toxicity as a future therapeutic strategy for obesity, as stated by the authors in the abstract. However, the main text primarily focuses on the types and advantages of nanotherapeutics, while the discussion of their limitations and challenges remains insufficient.

Minor 

1. Please cite Table 2. and Figure 5. in the text
2. It appears necessary to carefully check whether the in-text citation style follows the guidelines of the Journal of Nanotheranostics. According to the journal's instructions, square brackets should be used for citations; however, parentheses are currently used throughout the manuscript.

Author Response

Nanomedicine as a Promising Treatment Approach for Obesity

 

05/07/2025

We sincerely thank the reviewers for their constructive feedback, which has helped us improve the quality and clarity of our manuscript. We have carefully addressed each comment point by point, as detailed below. 

All changes made in response to the reviewers’ suggestions have been clearly highlighted in yellow in the revised manuscript for ease of reference.

Reviewer 2

 

Comments and Suggestions for Authors

Major

1. As this is a review article, the number of references is clearly insufficient. Typically, review articles are expected to include around 100 to 150 references to comprehensively cover the relevant literature.

               Reply: Additional references have been included; however, it is important to note that the topic is novel, and therefore the number of available references is limited.

 

2. Table 1 summarizes the description and disadvantages of each type of treatment. I would like to suggest that the advantages of each treatment type should also be included in the table for a more balanced and comprehensive comparison.

Reply: We thank the reviewer for the comment and agree with the suggestion. The advantages have been added in a separate column

3. This review article aims to explore the role of nanomedicine and its potential toxicity as a future therapeutic strategy for obesity, as stated by the authors in the abstract. However, the main text primarily focuses on the types and advantages of nanotherapeutics, while the discussion of their limitations and challenges remains insufficient.

Reply: In response to the reviewer’s comments, we have added a brief paragraph on page 5, line 216, to highlight key weaknesses in current nanomedicine research for obesity. Additionally, we have included a new subsection (Section 2.3: “Challenges Associated with Nanomedicines That Restrict Their Translation into Clinical Use”, page 15), which provides a more detailed discussion of the technological, clinical, and regulatory limitations. Furthermore, we have added remarks on the limitations of nanotherapeutic approaches in the Conclusion (page 16) to further strengthen the critical analysis of translational challenges.

 

Minor 

4. Please cite Table 2. and Figure 5. in the text

Reply: Table 2 and Figure 5 are cited in the text on lines 424 and 570, respectively.

5. It appears necessary to carefully check whether the in-text citation style follows the guidelines of the Journal of Nanotheranostics. According to the journal's instructions, square brackets should be used for citations; however, parentheses are currently used throughout the manuscript.

Reply: The reference style has been revised to comply with the journal's guidelines

 

Author Response File: Author Response.pdf