Review Reports

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

The authors introduced all of the reviewer's comments. The revised
version of the manuscript is now suitable for publication 

Author Response

Dear Reviewer, we sincerely thank you again for your comments, suggestions, and for the thorough review of our manuscript.

Attached, please find a document containing our responses to each of your observations.

Author Response File: Author Response.pdf

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

Some of the previous comments were addressed with  modifications in the text. However, this manuscript needs improvements. A thorough revision of the manuscript is still required. Please avoid unnecessarily lengthy descriptions and widely known background facts. Remove irrelevant text and unnecessary details to improve conciseness and focus. The length of the manuscript must be reduced by half.

1. Despite the revisions, the Introduction contains excessive textbook-level information (lines 44-64, 85-95, etc.). A clearly defined knowledge gap is still missing, and the specific novelty and contribution of the study are not explicitly stated.
2. Table 1 should be removed. The data it presents are fully redundant with the textual description in Section 1.1 and the visual documentation provided in Figure 2. Retaining the table adds no value and only lengthens the manuscript.
3. The paragraph spanning lines 214–230 is largely descriptive and repetitive; it should be condensed or removed to tighten the narrative and avoid stating obvious or previously reported observations.
4. Sections 2.1 and 2.2 should be rewritten in a concise, focused, and precise manner and substantially shortened. Moreover, the authors should focus on explaining the reasons behind the observed patterns rather than merely stating the facts, especially since many of these patterns are trivial (such as the effect of a stabilizer).

Author Response

Dear Reviewer, we sincerely thank you again for your comments, suggestions, and for the thorough review of our manuscript.

Attached, please find a document containing our responses to each of your observations.

Author Response File: Author Response.pdf

Reviewer 3 Report (Previous Reviewer 3)

Comments and Suggestions for Authors

I believe that the new version of the article Manuscript ID: ddc-4146359, supplemented in accordance with my comments in the first review, has been significantly improved and can be accepted in the new version for publication in the journal Drugs Drug Candidates.

Author Response

Dear Reviewer, we sincerely thank you again for your comments, suggestions, and for the thorough review of our manuscript.

Attached, please find a document containing our responses to each of your observations.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

The authors have made an effort to revise the manuscript in response to the previous review. However, the revisions addressing the remaining major comments are superficial and do not fully meet the reviewer's requests. The introduction remains overly descriptive, the problematic paragraph persists, and the results sections, while slightly trimmed, are still largely descriptive rather than analytical. A further, more focused revision is necessary before the manuscript can be considered for publication.

1. The introduction is still too lengthy and contains a significant amount of textbook-level information. The detailed descriptions of selenium's discovery, isotopes, oxidation states, and dietary sources are not necessary for the reader. A more concise background that quickly establishes the relevance of SeNPs and the specific challenges in their synthesis would be more effective. More importantly, the specific knowledge gap this study addresses is still not explicitly stated. You list your objectives, but you do not clearly articulate why this optimization is novel or necessary. What is missing from the current literature that your systematic investigation of these specific parameters (concentrations, time, PVA volume) provides? Please state this clearly.
2. The request to condense or remove the repetitive paragraph and to shorten Sections 2.1 and 2.2 has not been sufficiently addressed. While some sentences have been rephrased, the narrative remains largely descriptive. The manuscript would be significantly strengthened by focusing on explaining the reasons behind these observations. Sections 2.1 and, especially, 2.2 are excessively long and read like a lab notebook, describing observations step-by-step without sufficient analysis.
3. The discussion frequently states trivial or well-established facts, such as the role of PVA as a stabilizer preventing aggregation. The manuscript's strength lies in its detailed parametric study, but the discussion falls short of explaining the reasons behind the observed trends. For example, why does a higher PVA volume lead to a smaller hydrodynamic diameter and lower PdI specifically in purified samples? The authors demonstrate that purification is critical for stability in the presence of PVA and suggest that it removes impurities. However, they fail to explain how these impurities interfered with PVA’s function in the non-purified (WOP) samples. Did they hinder the adsorption of PVA onto the nanoparticle surface? Did they destabilize the colloid by affecting the ionic strength of the medium? A deeper discussion on this mechanism is needed. How does PVA, being a non-ionic polymer, influence the surface charge?
4. The manuscript in its current form does not effectively communicate its scientific contribution. The authors are encouraged to undertake a major revision focused on significantly tightening the narrative, removing redundancy, and deepening the mechanistic discussion. By addressing these issues, the paper will become a much stronger and more impactful contribution to the field.

Author Response

Dear Reviewer, we inform you that the document containing our responses to your comments has been duly attached. We sincerely thank you again for your valuable contributions. We have carefully addressed all the points raised and made substantial modifications to the manuscript, including significant revisions to both its content and structure. We hope that, with this revised version, the manuscript is now suitable for publication.

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

1. I strongly recommend clearly and unambiguously articulating the specific knowledge gap that your study fills. Instead of a general phrase about "a limited number of systematic studies," you must specify which particular parameters (e.g., the gradient of stabilizer volumes, the impact of purification on long-term stability) have not been previously investigated and what constitutes the novelty of your approach.
2. I welcome the authors' attempts to improve the manuscript, but I do not understand their persistent reluctance to make Sections 2.1 and 2.2 more concise. The work is overloaded with insignificant details; furthermore, the data are duplicated across tables, graphs, and photographs.
3. The literature contains numerous studies on the chemical synthesis of SeNPs using Na₂SeO₃ and AA, employing various stabilizers (chitosan, CMC, PEG, proteins) at different concentrations. However, the manuscript lacks a systematic comparison of the obtained synthesis results with previously published data, which significantly weakens the scientific discussion and obscures the novelty of the work.
4. The conclusion remains overly descriptive and lacks clear articulation of the study’s main scientific contribution. Some questions remain: What new understanding has been generated? How does this work advance reproducible SeNP synthesis or long-term stability control? The transition between physicochemical characterization and biological testing is abrupt, and the discussion of antifungal inactivity is insufficiently interpreted. The final statements about broader applications are somewhat speculative and would benefit from more cautious framing and stronger linkage to the presented data.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The author’s purpose of the paper about “ Selenium Nanoparticles: Influence of Precursors, Reducing and  Stabilizing Agents on Size, Morphology and Spectral Properties is very interesting also for related research fields.  Suggestions:

 

• The title should be short and concise, besides reflecting the results. A short title would eventually increase the citations of the paper. What is really new in the paper? The bioactivity of SeNp?
• The first sentence of the abs perhaps shopuld be not that one. A first sentence framing the paper is important. At the abs imprecise terms such as “ was less effective than”...should be avoided. But how much less? Quantitative values and amounts used and certain experimental coniditons should be referred for rapid comparion with similar studies with the same ot others metals np and/or microorganisms.
• Abbreviations should be defined at first mention in each of the following sections in your paper, such as PVA and AA.
• The results are not always properly described. The authors should first describe in a quantitative manner the data before jump to conclusions. Avoid expressions such as ….”greater (15 times), but how much greater?......increase (21 times) but how much?
• Significant was mention 24 times! Was the data validated by statistical analysis? If so, there is no need to refer that the values were “significant” or not sgnificant. However, the quantitative information about the decrease (or increase) is fundamental. The data should be described first. The reader should visualize the data after a correct description.
• At page 18: For comparison rpm should be given in xg not rpm. 9.000 rpm [80], 10.000 rpm [70,92], 12.000 rpm 561 [81] and with an increase in speed from 8.000 to 12.000 rpm [73], corroborating and justi-562 fying the high speed used in this study 13.000 rpm (24.300 g).
• What is the concentration due to 0.5 μg/mL of Fluconazole? What were the concentration of SeNP used?
• The authors concluded that: The SeNPs selected for antifungal activity assessment, after characterization, had no effect on planktonic cells of the SC5314 strain of albicans or on preformed biofilms, possibly due to the greater resistance conferred by the latter growth form. Is that correct? So no bioactivity was shown? Please clarify?

Reviewer 2 Report

Comments and Suggestions for Authors

The paper deals with the fabrication of selenium nanoparticles and determination of their antifungal activity using ascorbic acid as reducing agents.

The manuscript is poorly written and reads like AI-generated text. It is an overloaded draft with a stream-of-consciousness style and little focus on the key results. It resembles a rough preliminary version that requires careful reflection to identify the main ideas and eliminate redundant material. It should be reduced to approximately one third of its current length. The text contains many heavy, cumbersome sentences, as well as tautologies and repetitive structures ('previous studies have indicated...'; 'previous studies suggest...'; 'observed...'; 'observed...'), which further undermine its readability and scientific clarity.

Another important question for this work is the novelty of the manuscript. There are thousands of articles devoted to the synthesis of selenium nanoparticles. What new information does your article contribute to the existing literature on this topic? The Introduction does not provide the necessary context for the study: it contains a large amount of non‑essential and partly irrelevant information, while the key elements are missing. The Introduction should be substantially shortened by removing textbook‑level background on selenium, fungi, etc., and refocused on clearly defining the specific knowledge gap in the extensive literature on selenium nanoparticles and the precise contribution and novelty of the present study.

There are also too many figures and tables, many of which do not provide new information (table 1, fig. 9-10). These should be removed or merged so that only the most informative visuals supporting the key results remain. Instead, fig.9-10, a table must be provided with a clear indication of the molar (or mass) ratios of the reagents used in each of the experimental series, along with other key conditions such as temperature, pH, reaction time, and concentrations.

The authors should also clarify the discrepancy between the UV–Vis spectra and the visual appearance of the dispersions. In particular, for Figures 1–2, how do you explain the absence of significant absorption above 300 nm, and why do the recorded spectra not seem to correspond to the observed color of the selenium hydrosols?

Any comparison of the obtained data with the literature is lack. The discussion section should be improved. An improvement of the discussion is needed also in relation to similar or analogous results from literature and the explanation of possible differences.

Unfortunately, the scientific value of the manuscript is minimal. The article has serious flaws and additional experiments needed. I thus cannot recommend this paper for publication.

Reviewer 3 Report

Comments and Suggestions for Authors

This article is of interest to researchers and consumers of selenium nanoparticles (SeNPs) due to their lower toxicity compared to pure selenium, as well as their chemical stability, bioactivity, and biocompatibility.The authors stated that the goal of the study was to optimize the chemical synthesis parameters of SeNPs using Na2SeO3, AA, and APV to ensure the quality and stability of SeNP nanostructures. The article consistently outlines the steps to achieve this goal.

However, the submitted article is not without shortcomings, and in order to be published in the journal DDC, the authors must respond to the reviewer's comments in the text of the article and make the necessary additions and changes:

 1) Swap the two sections of the article following the first section, 1. Introduction, and present the article in the following order: 1. Introduction, 2. Materials and Methods, 3. Results and Discussion,         4. Conclusions.

 2) In Section 2. Materials and Methods, present the chemical reaction for the reduction of selenium Se from Na₂SeO₃ using ascorbic acid.

3) Describe the method for purifying WP SeNPs nanoparticles.

4) What are the reasons for the broadening of absorption bands (λmax) in the UV spectra and the decrease in their intensity in SeNPs WP samples (Fig. 1 and others)?

5) What are the black or orange precipitates at the bottom of the test tubes: what is their atomic composition, what chemical compounds are they, and what are their particle sizes?

6) When describing the role of PVA in the synthesis of WOP and WP SeNPs, provide the chemical formula of PVA and briefly describe the nanoparticle stabilization mechanism.

7) Why are the electron microdiffraction results for the electron beam passing through SeNPs not shown in Figure 7 along with the TEM micrographs? Only microdiffraction patterns (spotted from nanocrystals, or diffuse one or two rings from amorphous nanoparticles) can unambiguously determine the crystalline or amorphous state of the synthesized nanoparticles.

8) In section 4. Conclusion, emphasize the novelty of the results obtained.

 After the questions and comments posed in the text of the article have been answered and the revised version has been re-reviewed, the article may be published in the journal DDC.