A Novel One-Pot Synthesis of PVP-Coated Iron Oxide Nanoparticles as Biocompatible Contrast Agents for Enhanced T₂-Weighted MRI

Round 1

Reviewer 1 Report

Generally a nice paper, but somewhat lacking in novelty. 

Please refer to this paper as well:

A model of lysosomal metabolism of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles: implications for cellular magnetic resonance imaging - PubMed (nih.gov)

MRI detection of single particles for cellular imaging - PubMed (nih.gov)

Nanomaterials | Free Full-Text | Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes (mdpi.com)

Figure 3 (the pictures still need to be revised (look stretched), please make sure they are ok). Figures 4 and 5 need to be improved (we recommend using Orign or Prism, not Excel).

The study lacks a basic biological evaluation. The particles need to be tested for biocompatibility (blood and/or endothelial cells).

Author Response

Dear Reviewer,

We would like to express our gratitude for your positive feedback and comments on our manuscript. Your insightful comments and suggestions have been greatly appreciated and have helped us to improve the quality and clarity of our work. We are pleased to note that you find our research significant and recommend it for publication, once your insightful comments are properly addressed.

We have carefully reviewed your comments and have taken all necessary steps to address your concerns. We have responded to all questions/comments raised by the reviewers and have amended the manuscript accordingly, as listed below. We believe that the revised manuscript is now more precise and suitable for publication in the Journal of Composites Science.

Thank you for your contributions to our manuscript, and we hope that you find the revised manuscript acceptable for publication. If you have any further suggestions or comments, please do not hesitate to let us know.

Yours sincerely,

Tariq AlZoubi (on behalf of all authors)

Author Response File: Author Response.docx

Reviewer 2 Report

The authors discuss the synthesis and characterization of polyvinylpyrrolidone coated magnetite nanoparticles as contrast agent for magnetic resonance imaging applications. I think the paper is appropriate for publication in Journal of Composites Science. However, before, I suggest some minor corrections in order to improve the article quality.

11)      In the abstract, the acronyms PVP is used, without giving a definition of it. This definition is only provided later, in the body of the article. The abstract should be understandable by the reader. By the way, in the text such definition is provided several times (2 times in line 62, then in lines 103, 115, 202). Once is enough.

22)      Still in the abstract, when anticipating the results for PVP-40K, again, it is not clear what “40K” means. Also, it is said that it has “ … a narrow size distribution (11.61 nm)”. Clearly, the number refers to the average size, not to the distribution. It may be stated more precisely.

33)      In the keywords, I would rather use either “Superparamagnetism” or “Superparamagnetic particles”.

44)      In line 39 there is a sentence starting with “These agents”. The term “contrast agents” is not introduced yet in the previous sentence. There is only a generic reference to contrast. People not familiar with MR imaging may not be aware that this is achieved using contrast agents.

55)      In Sect. 2.2, line 145, sample A is defined as a PVP-SPION sample. Later in the text my understanding is that the first sample is just a bare SPION sample, without coating. Could the authors be precise on this point?

66)      Also, the other 3 samples are said to be synthesized with PVP-10000, PVP-25000, PVP-40000. What do exactly these numbers mean?

77)      In Sect. 2.4., line 164, it is said that MR relaxation experiments were obtained by mixing Fe at different concentrations. I believe that nanoparticles are mixed rather than just iron.

88)      Sects. 3.1, 3.4, 3.5 begin with “This The …”. Please, revise this misprinting.

99)      Line 199 is a repetition of line 197.

110)   In line 202 it is said that “ … PVP, did not affect the phase change of the Fe3O4 nanoparticles”. What phase change is referred to? Or, do the authors mean that “ … PVP, did not induce a phase change of the Fe3O4 nanoparticles” ?

111)   In the caption of Figure 3, I believe that the samples are not reported in the right order. Probably (B) and (D) must be inverted.

112)   The sizes reported in sect. 3.2 are never compared to those obtained from the Scherrer equation in sect. 3.1. I think a brief comment would be required.

113)   In line 327, the referred figure should be Fig. 5, not Fig. 6.

114)   In the same line it is said that there is no remanence and coercivity for all samples. However, since the authors report the inset with an enlargement of the low field interval, the PVP-40K sample shows some small hysteresis. Since it is shown, the authors could just add a comment on that.

115)   In line 332, it is said that “ … the nanoparticles are well protected from oxidation …”. Actually, magnetite is already an oxide. Probably the authors meant "phase change" or "amorphization".

116)   Values of magnetization are given in emu/g. Is it the weight of the overall particles, or has the PVP weight been subtracted? Is the last component significant? Some comment may be useful.

117)   In Fig. 5 caption, it is said that “The inset represents the magnetic behavior of all investigated samples in the absence of the applied magnetic field”: This is not correct of course, since the applied field is reported in the x-axis. It is just the low field behavior in order to evidence the presence of remanence/coercivity.

118)   Lines 363-373 are confusing. First it is said that an increase of surface area increases magnetization (lines 363-364). This is absolutely not true! Well separated particles do not provide higher magnetization. The contrary actually may occur, if surface effects are relevant (as stated just two lines later!). In lines 368-370 it is said that reduction of the size increases the thickness of the outer shell. This is not correct, also. It is only the fraction of sample contained in the outer shell that increases proportionally, with respect to the core fraction. The thickness is almost constant. Moreover, there is not really such a strong variation of particle size that justifies such different saturation between PVP40K and the other samples. It would be interesting to renormalize the different magnetization curves in order to superimpose them and verify if they all have the same “shape”. If there were a relevant size dependence, this should be reflected also in the shape. Larger particles have steeper initial magnetization trend and they tend to saturate at smaller fields. See for example, Journal of Applied Physics 105, 083924 (2009).

119)   Lines 374-388 are just a repetition of the previous sentences.

I ask the authors to consider my suggestions in order to obtain an improved version of their report.

Author Response

Dear Reviewer,

We would like to express our gratitude for your positive feedback and comments on our manuscript. Your insightful comments and suggestions have been greatly appreciated and have helped us to improve the quality and clarity of our work. We are pleased to note that you find our research significant and recommend it for publication, once your insightful comments are properly addressed.

We have carefully reviewed your comments and have taken all necessary steps to address your concerns. We have responded to all questions/comments raised by the reviewers and have amended the manuscript accordingly, as listed below. We believe that the revised manuscript is now more precise and suitable for publication in the Journal of Composites Science.

Thank you for your contributions to our manuscript, and we hope that you find the revised manuscript acceptable for publication.

Yours sincerely,

Tariq AlZoubi (on behalf of all authors)

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The produced particles must be tested for toxicity. At least on a suitable cell line like T-cells or endothelials Without this, the article cannot be published. 

Author Response

Dear reviewer,

Thank you for taking the time to review our manuscript and for providing your valuable feedback. We greatly appreciate your insightful comments and suggestions which have helped us to improve the quality of our work.

We are pleased to inform you that we have carefully considered all your comments and concerns, and have made the necessary revisions to the manuscript as per your suggestions. We have also provided detailed responses to all the questions and comments raised by you.

We are confident that you will find the revised version of the manuscript to be suitable for publication in the Journal of Composites Science after incorporating all the requested modifications. We sincerely hope that all the appropriate changes have been made and that the manuscript is now more precise and suitable for publication.

Once again, we would like to express our gratitude for your time and effort in reviewing our manuscript. We look forward to your positive feedback on the final revised version.

 Sincerely,

Tariq AlZoubi (on behalf of all authors)

Associate professor of Physics

College of Engineering and Technology

American University of the Middle East

Author Response File: Author Response.docx

Reviewer 2 Report

This are my comments on the authors responses.

 

Point 7) has not been amended, although the authors agreed with my comment.

It is not clear the response to point 10). Is there a phase change? In fact, “…did not affect the phase change…” means that Fe3O4 particles undergo a transition to a different phase anyway, but this phase change is the same whether there is a coating or not.

Regarding point 14), I believe that now hysteresis is not evident just because the curve is partially hidden by the other curves, and the line is thicker. I would have just commented that there is a small, but negligible, hysteresis, instead.

Regarding point 15) the authors agree that their sentence is not accurate. However, they did not correct the manuscript appropriately. See also point 18) below.

The authors answered to my point 16) but I couldn’t find this piece of information in the emended manuscript. Also other readers could have the same doubt.

In the amendment of point 18) there are two contradictory sentences: “In bare SPIONs, magnetite can easily oxidize to maghemite during the washing process [25], thereby the Ms value of bare SPIONs is affected. Furthermore, the observed Ms value suggests that the nanoparticles are well protected from oxidation”. It is not clear if there is or there is not oxidation. See also point 15 above.

Author Response

Dear reviewer,

Thank you for taking the time to review our manuscript and for providing your valuable feedback. We greatly appreciate your insightful comments and suggestions which have helped us to improve the quality of our work.

We are pleased to inform you that we have carefully considered all your comments and concerns, and have made the necessary revisions to the manuscript as per your suggestions. We have also provided detailed responses to all the questions and comments raised by you.

We are confident that you will find the revised version of the manuscript to be suitable for publication in the Journal of Composites Science after incorporating all the requested modifications. We sincerely hope that all the appropriate changes have been made and that the manuscript is now more precise and suitable for publication.

Once again, we would like to express our gratitude for your time and effort in reviewing our manuscript. We look forward to your positive feedback on the final revised version.

 Sincerely,

Tariq AlZoubi (on behalf of all authors)

Associate professor of Physics

College of Engineering and Technology

American University of the Middle East

Author Response File: Author Response.docx

Round 3

Reviewer 1 Report

Thank you for including the cytotoxicity assay.  Pleas add a paragraph how the assay was carried out to the Materials part.

Reviewer 2 Report

The authors have answered appropriately to all my suggestions and doubts.