While the review on "Understanding the multidrug resistance paradigm of cancer and the
application of nanomaterial based photodynamic therapy for cure" is a contemporary topic; the entire section, from the introduction to the limitations of PDT, seems to be a repetitive version from old publications on PDT. Figures 1 and 2 are also outdated, lacking modern relevance. Figure 2 is a weaker version of Figure 3 of the review entitled: Photodynamic Therapy for the Treatment and Diagnosis of Cancer–A Review of the Current Clinical Status (https://doi.org/10.3389/fchem.2021.686303). To address these weaknesses, the following points should be considered:

1. The review overlooks the role of third-generation tetrapyrrolic macrocycles as photosensitizers (PSs), which have significantly advanced PDT. These contemporary PSs have revolutionized the field with their efficient drug delivery mechanisms, ability to promote apoptosis, and capability to elicit post-PDT immunogenic responses for cancer therapy.

2. The detailed figures and the typical Jablonsky description of PDT are repetitive and have been extensively reported in previous literature. It would be beneficial to present a more updated version of PDT instead.

3. Exploring the roles and mechanisms of action of various nanoparticles and their composites with tetrapyrrolic macrocycles would provide a more contemporary view of progress in drug development related to nanocomposites. This aspect has been lacking in the present review.

4. Including examples of nanomaterials approved by regulatory agencies such as the FDA and successfully cleared clinical trials for anticancer PDT would be valuable. This information would draw attention to the biosafety of certain nanomaterials and their potential as potent alternatives to commercial drugs.

5. The review lacks adequate research and reporting on the toxicity and threats associated with the synthetic means employed in PDT and strategies to overcome these challenges.

6. The section dedicated to gold nanoparticles (AuNPs) and silicon nanoparticles (SiNPs) is insufficient and fails to represent the extensive research outcomes reported in the literature on these topics.

7. The review does not include an essential aspect of porphyrin-fullerene dyads and their significance in antineoplastic applications. Incorporating this information would enhance the comprehensiveness of the review.

8. The review has numerous typographical errors, and the language used lacks vibrancy and impact. The title itself requires improvement.

Addressing these points would enhance the quality and relevance of the review, providing a more comprehensive and up-to-date understanding of the topic. Graphical representations, cartoons/bar charts on the various photobiological outcomes, and recently published structures of nanocomposites will attempt to be impactful in comparison with the many reviews already available in the literature.

While the revised version of the manuscript represents an improvement over its initial iteration, there remain several unresolved issues:

1. The assertion that "Porphyrins, chlorins, bacteriochlorins, are among the most promising third-generation tetrapyrrolic macrocycles" is inaccurate. Foscan, tookad, purlitin, and many other tetrapyrrolic macrocycles belong to the second generation of Photosensitizers (PSs). Even the description provided in response does not pertain to third-generation PSs but second-generation PSs.
2. The manuscript contains typographical errors throughout and requires further language refinement.
3. A comprehensive review of PDT necessitates the inclusion of a diverse array of structures of contemporary photosensitizers or nanohybrids reported to qualify as more efficient third-generation PSs.
4. The notations for C60 and C70 should be appropriately denoted as C60 and C70.
   There needs to be more clarity in introducing each agent contributing to PDT by influencing the photosensitizer.
5. Figure 4 requires a thorough review and potential revision.
6. The headings and subheadings in the manuscript need a compelling presentation. Specifically, Heading 2 should be revised to "Photodynamic Therapy" rather than "Photo dynamic Therapy" to ensure accuracy and clarity.
7. Light dosimetry has not been addressed, and it is essential to justify the dosimetry of the light utilized in the articles cited in the review. PDT can only be considered complete by thoroughly discussing and explaining this crucial aspect.