Nanocarriers Responsive to Light—A Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript provides a comprehensive review of the applications of light-responsive drug carriers in cancer and other diseases, particularly focusing on photodynamic therapy (PDT) and photothermal therapy (PTT). The innovative aspect of this study lies in combining photosensitive nanocarriers with other treatment modalities to overcome the limitations of conventional chemotherapy, offering more precise and non-invasive therapeutic approaches, which serves as a valuable reference for academia. However, the following areas require further refinement:

1.The review leans heavily towards introducing the functionalities of light-responsive drug carriers, lacking in-depth analysis of current research progress.

2.There is limited discussion on the clinical applications and challenges of light-responsive systems. It is recommended to include a section on clinical translation barriers and potential solutions.

3.It would be beneficial to delve further into the practical application challenges and future research directions of light-responsive carriers, enhancing the practicality and readability of the study.

4.Figures 1 and 2 illustrating mechanisms are overly simplistic; enriching the content of these images would align them better with the standards for journal publication.

Author Response

please find the attached response to all reviewers' comments.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Line 54 – Some individual citations would be helpful here in addition to citing the Review by Lai

Line 65/Table 2 – Important to distinguish between type of light, for example, continuous wave vs ultrafast laser irradiation as they have very different responses (see Trout et al - https://pubs.rsc.org/en/content/articlelanding/2021/nj/d1nj02062e)

Line 84/Table 3 – It would be helpful to provide individual references for the items in the table. For example , for Liposomes, Eloy et al - https://www.sciencedirect.com/science/article/abs/pii/S0927776514005001

and Hines et al for PLGA - https://pmc.ncbi.nlm.nih.gov/articles/PMC3719420/#:~:text=PLGA%20is%20the%20most%20successful,develop%20new%20controlled%20release%20systems.

I am curious to why the table has a row specifically for PLGA rather than polymersomes, when in the above rows it has more broad categories such as liposomes and micelles and not individual lipids etc

Line 85 – The discussion on inorganic NPs should be expanded and cite more than one review. This is a large field and the properties are very different depending on the type of inorganic NP. “Toxicity concerns, even if reduced” is unclear.

Line 92 – Perhaps the “polymeric nanoparticle section would fit better as a subheading under the broad organic nanoparticle category

Line 101 – this comparison might be more clear with a figure

Table 6/ Line 103 – Citations should be provided for each application

Table 8/Line 447: I believe this table would be easier to follow if the Materials and Design column were split into two. Perhaps a column detailing the light activation would be helpful since that is the focus of this review.

Author Response

Please find the attached file for the response to all the reviewers' comments.

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

The introduction could more thoroughly address current challenges associated with traditional drug delivery methods before transitioning to a discussion of the advantages of light-responsive systems.

Please enhance the clarity of the section comparing different types of nanoparticles, clearly presenting their respective advantages and disadvantages. Additionally, it would be interesting to see a more detailed discussion of clinical challenges and practical applications, especially concerning long-term safety and biocompatibility.

In the section on the synergy between photodynamic therapy and photothermal therapy, it would be beneficial to provide a more detailed explanation of how these therapies work together to enhance treatment effectiveness.

The descriptions of in vitro and in vivo studies could be better organized—highlighting differences in results and their implications for clinical applications would strengthen the discussion.

Comments on the Quality of English Language

1. Dividing longer sentences into two or more shorter ones can improve clarity, particularly in the sections describing the mechanisms of PDT and PTT.

2. Consistent use of terms, especially technical ones (e.g., "photothermal agents," "light-triggered drug release"), would help avoid potential misunderstandings.

3. Some descriptions, particularly those in the sections on materials and methods, could be made clearer by restructuring sentences or adding brief definitions for specialized terms.

Author Response

Please find the attached file with answers to all the reviewers' comments.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I do not other concerns, thank you for your revision, and good luck.