The Role of p53 in Nanoparticle-Based Therapy for Cancer

Round 1

Reviewer 1 Report

This is a review paper.

This review presents the latest advancements in this field of biomedical research and explores innovative strategies to address the challenges associated with p53-targeting nanomedicine.

Overall, this review serves as a valuable resource for researchers seeking insights into p53-targeting nanomedicine.

The authors are also advised to consider the following suggestions to further improve this review.

(1)    Please avoid lumped references.

(2)    Please improve the figure quality.

(3)    The authors suggest to add an additional section called “6. Summary and conclusions”. In section 5, please change it to “Limitations and future perspectives”. This is because the final section usually do not have citations.

(4)    Please further polish the writing. The first draft still has grammar mistakes and typo errors.

The writing needs to be further polished.

Author Response

Response to the Reviewer 1:

According to the Reviewer’s suggestions:

Please avoid lumped references.

We have tried to remove repeated references to reduce the number of clustered citations.

Please improve the figure quality.

The figures were downloaded for the second time with 600 dpi and sent with the corrected manuscript to the editorial board.

The authors suggest adding an additional section called “6. Summary and conclusions”. In section 5, please change it to “Limitations and future perspectives”. This is because the final section usually does not have citations.

We are grateful for this remark. We have changed the structure as suggested.

Please further polish the writing. The first draft still has grammar mistakes and typo errors.

We have corrected those typos we were able to find. Thank you for drawing attention to this weakness.

Reviewer 2 Report

The manuscript provides a detailed overview of the role of p53 in cancer and the potential use of nanoparticle-based therapy in restoring p53 function. It covers various aspects, including the biology of p53, its role in cancer, the limitations of current p53-targeted therapies, and the use of nanoparticles for gene delivery. It also offers a lucid explanation of the bystander effect, a significant concept in p53-related therapy. This adds depth to the discussion and helps readers grasp the potential benefits of p53-targeted therapy.

There are some points that may need attention:

1.       While providing background information is important, the introduction section is quite lengthy and detailed. A more concise introduction, focusing on key points and swiftly transitioning to the primary topic of nanoparticle-based therapy, would enhance the reader's engagement.

2.       The manuscript briefly touches upon the challenges associated with Mdm2 inhibitors. However, a more in-depth exploration of the obstacles and limitations in the development and clinical application of p53-targeted therapies, particularly in the context of nanoparticle-based approaches, is needed.

3.       The manuscript introduces several technical terms and acronyms (e.g., DDC, DOPE, Chol, DOTAP, PLGA, PLA) without adequate explanations. Providing definitions or clarifications for such terms would enhance the manuscript's accessibility to a wider readership.

4.       While Gendicine is briefly mentioned in the abstract section, its significance and relevance are not adequately explored in other parts of the manuscript, warranting a more comprehensive discussion.

The manuscript is well-crafted. However, there is a need for minor English corrections, as evident in line 398.

Author Response

Response to the Reviewer 2:

According to the Reviewer’s suggestions:

While providing background information is important, the introduction section is quite lengthy and detailed. A more concise introduction, focusing on key points and swiftly transitioning to the primary topic of nanoparticle-based therapy, would enhance the reader's engagement.

According to the reviewer’s request, the introduction section was shortened for brevity.

The manuscript briefly touches upon the challenges associated with Mdm2 inhibitors. However, a more in-depth exploration of the obstacles and limitations in the development and clinical application of p53-targeted therapies, particularly in the context of nanoparticle-based approaches, is needed.

An additional section was included in the final version of the manuscript to discuss the disadvantages of adenovirus-mediated p53 vectors.

The manuscript introduces several technical terms and acronyms (e.g., DDC, DOPE, Chol, DOTAP, PLGA, PLA) without adequate explanations. Providing definitions or clarifications for such terms would enhance the manuscript's accessibility to a wider readership.

Explanations have been added in the bottom footnotes. We are grateful for bringing this issue to our attention, as it may indeed be difficult for readers not familiar with the subject.

While Gendicine is briefly mentioned in the abstract section, its significance and relevance are not adequately explored in other parts of the manuscript, warranting a more comprehensive discussion.

We have added a mention of gendicine in the introduction to chapter 2 and in chapter 6. Thank you for bringing this to our attention. 

Reviewer 3 Report

This article on the affects of p53 and cancers is very well written overall with just minor corrections of english neccessary. The authors do a good job of mixing background information with the missing links currently in the literature (prime example lines 103-106 where they describe why mdm2 inhibitors are still lacking in therapy. There is only one major problem which I will discuss below. I suggest these corrections for this article to be published

-minor english corrections that will be caught by mdpi during publication

-organization of sections. I dont know the format for this template but the separation of the intro into two parts followed by 2 2.1 etc seems awkward. I ask to check template regulations

Major

-The authors have done a great job at looking at the benefits but also the negatives of p53 research; however, the literature base is severely lacking. In the section of liposomes they give 2 citations, same with polymers. Mettalic NPs they give more examples but still. Then the authors go on to talk about toxicity but only stress the metallic  nps in that section while polymeric and lipidic toxicities are not discussed much.

-In addition to the previous comment. 91 citations where only a few are as recent as 2020 o r newer. p53 is and will be very important. The authors have greatly neglected recent resesarch in this field that is overflowing with possibilities to discuss in the scope of this paper

minor erros with articles etc. but minor.

Author Response

Response to the Reviewer 3:

According to the Reviewer’s suggestions:

The authors do a good job of mixing background information with the missing links currently in the literature (prime example lines 103-106 where they describe why mdm2 inhibitors are still lacking in therapy.

We added references to this part of the text.

organization of sections. I dont know the format for this template but the separation of the intro into two parts followed by 2 2.1 etc seems awkward. I ask to check template regulations.

We are grateful to the Reviewer for raising this issue. We have reduced the size of the introduction to avoid such a split.

The authors have done a great job at looking at the benefits but also the negatives of p53 research; however, the literature base is severely lacking. In the section of liposomes they give 2 citations, the same with polymers. Metallic NPs give more examples but still. Then the authors go on to talk about toxicity but only stress the metallic nps in that section while polymeric and lipidic toxicities are not discussed much.

Our focus was on the cytotoxicity of metal NPs because depending on the type of metal used to create the nanoparticles, the toxicity will develop in a different direction. As advised, we have expanded on the toxicity of liposomes and polymers with recent reports.

In addition to the previous comment. 91 citations where only a few are as recent as 2020 o r newer. p53 is and will be very important. The authors have greatly neglected recent resesarch in this field that is overflowing with possibilities to discuss in the scope of this paper.

Thank you for drawing attention to this fact. We have increased the number of references from 2020-2023 from 19 to 28 (28,5% of all references)

Round 2

Reviewer 3 Report

My previous claim still remains... Its a review article that is focusing on recent advances and should include expert opinions on the current status of the field etc. 28 % of the articles being in the last 3 years is underwhelming. Even if many citations fall in the intro there are neweer articles that could be used and numerous reviews on the topic. If the authors wanted to focus on the Metallic NPs they could have did the full article on that alone being more directed. 

no update

Author Response

Response to the Reviewer 3:

According to the Reviewer’s suggestions:

My previous claim still remains... Its a review article that is focusing on recent advances and should include expert opinions on the current status of the field etc. 28 % of the articles being in the last 3 years is underwhelming. Even if many citations fall in the intro there are neweer articles that could be used and numerous reviews on the topic.

We have tried to increase the number of new citations, as suggested. Now is nearly 40%.

If the authors wanted to focus on the Metallic NPs they could have done the full article on that alone being more directed.

We appreciate the reviewer highlighting this, we tried to find and mention one more article about the side effects of polymers and liposomes to balance. As for metal nanoparticles, we have already written two articles regarding them: PMID: 35743130 and PMID: 36365105.