Modulation of the Tumor Stroma and Associated Novel Nanoparticle Strategies to Enhance Tumor Targeting
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsIn this review, various approaches to improve drug penetration, such as the regulation of tumor vasculature, depletion of stromal proteins, and strategies targeting stromal cells, are discussed. The effectiveness of these methods is examined, emphasizing the need for further research and clinical applications to determine their impact on different tumor types. Currently, in the field of cancer therapy, a significant focus lies on how to regulate or normalize the tumor microenvironment (TME) to enhance drug penetration into tumors. This is considered a suitable theme for the review, highlighting the importance of ongoing research and clinical applications in addressing drug penetration into tumors.
While the overall content seems informative and organized, there are some potential issues or areas that could be further addressed:
While the paper discusses various strategies for enhancing drug delivery, a critical evaluation of the effectiveness of these strategies and potential limitations would add depth to the analysis. Are there any known drawbacks or challenges associated with the proposed methods?
The paper could discuss the practical applicability of the proposed strategies in clinical settings. Are these strategies currently being tested in clinical trials? What are the potential implications for cancer patients?
The paper concludes by emphasizing the need for further research, but it would be beneficial to explicitly outline specific areas for future investigation. What are the key unanswered questions, and how could future studies address these gaps in knowledge?
By addressing these points, the manuscript could become more reader-friendly and provide a more comprehensive exploration of the challenges and potential solutions in the field of drug delivery for solid tumors.
Comments on the Quality of English LanguageMinor editing of English language required
Author Response
Please see attached file.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe article is dedicated to the review of modulation of the tumor stroma to enhance the efficacy of current cancer treatments, which is a very important task nowadays. The review includes a description of three approaches to enhance drug delivery to the tumor: modulation of the tumor vasculature, altering extracellular matrix proteins to reduce interstitial fluid pressure, and normalizing or modulating tumor stromal cells. It is an interesting and important topic. But I have a few questions and comments about text:
The authors report the novel nanoparticle strategies to enhance tumor targeting. However, the references contain the most recent article of 2020. It is necessary to add more up-to-date data concerning this problem, especially if they write about novel strategies.
I think that the figure 1 is not successful. The figure shows the factors influencing flow of fluid and particles across capillaries, but it is unclear what is the result of all these pressures. In addition, the magnitudes of displayed pressures differ at the arterial and venous ends of the capillary, respectively, and the direction of the resulting force, too.
Author Response
Please see attached file.
Author Response File: Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsThe review is clear well organized and pleasant to read. The figures are very helpful to synthesize and fix information. The different aspects of the modulation of the tumor stroma are well covered.
I noticed that the more recent publications in the réferences are 2019, I was wondering if some more updated data, specially on novel nanoparticle strategies or systemic administration of plasmids were not published over the last three years (between 2020 and 2023. )
Author Response
Please see attached file.
Author Response File: Author Response.pdf
