Review Reports - Photodynamic Therapy Review: Past, Present, Future, Opportunities and Challenges

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors write an article for “The photodynamic therapy review: past, present, future, opport unities and challenges”. I have several comments for this topic:

(1) In the abstract, it is usually including a brief introduction, methods, results, and conclusions.

(2) Regarding to Introduction, it can delete the “Summary of PDT”.

(3) Suggest the Types I and II reactions in the introduce can write in the “Mechanism of PDT”. Please well organize the introduction part.

(4) Recommend the authors write the “light” part and then “Photosensitizer”. Writing the photosensitizer first is a little bit strange because light activated the PS to undergo the photochemistry reactions.

(5) For the limitations of PDT, please discuss them in detail. Why PDT is not applicable for treating metastatic cancer? Are there any future aspects for this?

(6) The sub-title “Nanoparticles in Antimicrobial Photodynamic Therapy (aPDT)”, Why this is Nanoparticles in Antimicrobial Photodynamic Therapy (aPDT)? The authors describe the function of nanoparticles in this paragraph, but do not explain briefly “What is Antimicrobial Photodynamic Therapy (aPDT)?” Suggest the sub-title change to “Antimicrobial Photodynamic Therapy (aPDT)”.

(7) Recommend the authors discuss clearly the future, opportunities and challenges that refer to the topic.

(8) Please italic the Staphylococcus aureus, Pseudomonas aeruginosa, etc. Some exist in the short form of “S. aureus”, please be consistent.

(9) Please well organize the manuscript and check the grammatical mistakes.

Author Response

(1) In the abstract, it is usually including a brief introduction, methods, results, and conclusions.

We thank the reviewer for this constructive comment. We understand the concern regarding the abstract. However, since this manuscript is a review paper, the current abstract format is intended to provide a comprehensive overview of the existing literature and the study's focus. We believe this approach aligns with the goals of a review paper, which aims to summarize and contextualize findings rather than presenting new experimental results. We appreciate your understanding of this perspective.

(2) Regarding to Introduction, it can delete the “Summary of PDT”.

Thank you for your feedback. We agree with your comment and have removed the "Summary of PDT" section as suggested.

(3) Suggest the Types I and II reactions in the introduce can write in the “Mechanism of PDT”. Please well organize the introduction part.

The authors agree with this comment and have moved the discussion on the mechanism, as suggested.

(4) Recommend the authors write the “light” part and then “Photosensitizer”. Writing the photosensitizer first is a little bit strange because light activated the PS to undergo the photochemistry reactions.

Thank you again for your insightful comment. We have revised the section to ensure that the discussion on photosensitizers precedes the section on light. This rearrangement aims to enhance the clarity and flow of the content.

(5) For the limitations of PDT, please discuss them in detail. Why PDT is not applicable for treating metastatic cancer? Are there any future aspects for this?

We sincerely thank the reviewer for highlighting this important discussion. We have expanded the limitations of PDT to cover selective accumulation, oxygen deficiency in certain tumor areas, resistance development, and challenges in determining optimal conditions. Additionally, we have included a discussion on the applicability of PDT for metastatic cancer and its future prospects. We believe these additions enhance the manuscript, and we appreciate the valuable feedback.

(6) The sub-title “Nanoparticles in Antimicrobial Photodynamic Therapy (aPDT)”, Why this is Nanoparticles in Antimicrobial Photodynamic Therapy (aPDT)? The authors describe the function of nanoparticles in this paragraph, but do not explain briefly “What is Antimicrobial Photodynamic Therapy (aPDT)?” Suggest the sub-title change to “Antimicrobial Photodynamic Therapy (aPDT)”.

The section on nanoparticles in antimicrobial PDT has been updated to focus on adjuvants in PDT. In response to concerns and advice from other reviewers, this section now covers a broader range of applications beyond antimicrobial PDT.

(7) Recommend the authors discuss clearly the future, opportunities and challenges that refer to the topic.

We have added a section titled "The Future, Opportunities, and Challenges of Photodynamic Therapy (PDT)" to the manuscript as recommended. This addition provides a clear discussion of the future directions, opportunities, and challenges related to the topic.

(8) Please italic the Staphylococcus aureus, Pseudomonas aeruginosa, etc. Some exist in the short form of “S. aureus”, please be consistent.

Formats of names of microbial species are corrected

(9) Please well organize the manuscript and check the grammatical mistakes.

We have reorganized the manuscript and thoroughly checked for grammatical mistakes. The revised version addresses the concerns raised by the reviewers and improves the overall clarity and readability of the content.

The authors would like to thank the two reviewers again. We believe that all concerns raised have been addressed in the revised version of our manuscript. We are confident that the manuscript is now significantly improved in terms of concept, technical content, and clarity of exposition. We look forward to hearing from you.

Sincerely,

Ali Oguz Er

Reviewer 2 Report

Comments and Suggestions for Authors

Photodynamic therapy (PDT) is a medical treatment that uses photosensitizing agents in combination with light to produce reactive oxygen species (ROS) that kill targeted cells, such as cancer cells and pathogenic microorganisms. Upon exposure to a specific wavelength of light, the photosensitizer is activated and generates ROS, leading to the destruction of nearby cells. This review covers the fundamental principles and mechanisms of PDT, detailing the critical components required for its function. It also examines the current clinical applications of PDT and potential future developments in the field. This review still has considerable room for improvement before publication.

1. This review focuses heavily on the antibacterial applications of PDT. As PDT is also widely used for treating cancer, fungi, and viruses, it would be beneficial to introduce these other applications to provide a more balanced perspective.

2. The mechanism of PDT is described multiple times (Lines 36-47, 273-282, and 284-295). To enhance clarity and maintain the reader's interest, I recommend consolidating these sections to avoid repetition and make the explanation more intuitive and engaging.

3. In Lines 251-253, the statement that “Tumor hypoxia is a major driver for cancer aggressiveness and is associated with stabilization of hypoxia inducible factor-1 (HIF-1), which regulates the expression of genes involved in tumor progression, aggressiveness, and metastasis” requires a citation. Please add appropriate references to support this claim.

4. The discussion of PDT materials (such as nanoparticles) comes immediately after outlining the limitations of PDT, which feels abrupt. A brief summary or transitional paragraph could help guide the reader smoothly into the next section.

5. The review currently lacks coverage of the excellent organic photosensitizers used in antibacterial and anticancer applications. Including a section on these would significantly enhance the comprehensiveness of the review.

Comments on the Quality of English Language

No.

Author Response

This review focuses heavily on the antibacterial applications of PDT. As PDT is also widely used for treating cancer, fungi, and viruses, it would be beneficial to introduce these other applications to provide a more balanced perspective.

We have added a section about cancer, fungi and viruses starting in line 650 and 790.

The mechanism of PDT is described multiple times (Lines 36-47, 273-282, and 284-295). To enhance clarity and maintain the reader's interest, I recommend consolidating these sections to avoid repetition and make the explanation more intuitive and engaging.

Thank you for pointing out the issue of repetition. We have addressed this problem and taken steps to ensure that it is resolved. The revised version of the manuscript now avoids unnecessary repetition and presents information in a more concise and streamlined manner.

In Lines 251-253, the statement that “Tumor hypoxia is a major driver for cancer aggressiveness and is associated with stabilization of hypoxia inducible factor-1 (HIF-1), which regulates the expression of genes involved in tumor progression, aggressiveness, and metastasis” requires a citation. Please add appropriate references to support this claim.

Additional references have been added to the manuscript as requested by the reviewer.

The discussion of PDT materials (such as nanoparticles) comes immediately after outlining the limitations of PDT, which feels abrupt. A brief summary or transitional paragraph could help guide the reader smoothly into the next section.

We thank the reviewer for this useful critic. To address the concern about the transition between the discussion of PDT limitations and the materials used in PDT, we have added a brief summary and transitional paragraph. This addition helps guide the reader smoothly from the limitations to the subsequent discussion on PDT materials, such as nanoparticles, ensuring a more cohesive flow in the manuscript.

The review currently lacks coverage of the excellent organic photosensitizers used in antibacterial and anticancer applications. Including a section on these would significantly enhance the comprehensiveness of the review.

We have added a new section covering the organic photosensitizers used in antibacterial and anticancer applications in page 6. This addition provides a more thorough overview of the advancements in this area and significantly enriches the review's content. We n