PONE-D-20-26378

Polystyrene sulfonic acid coated magnetic nanoparticles based extracellular and intracellular intermittent magnetic fluid hyperthermia treatment on the SK-Hep1 hepatocellular carcinoma cells

PLOS ONE

Dear Dr. Yao,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Yi Cao

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript was mainly focused on polystyrene-sulfonic-acid-coated magnetic nanoparticles and the magnetic fluid hyperthermia treatment on tumor cells. The study was interesting and some meaningful for clinical cancer thermo-treatment application. In addition, the synthesis process, characteristic and evaluation in vitro was abundant and well-founded. Generally the paper is recommended for publication in PLOS ONE after minor revision. There are several questions as follow:

1. All the manuscript should better be checked carefully with some problems with grammar and narration.

2. Compared with other researches, what's the advantage of the author's work? For the copolymer polystyrene sulfonic acid, what role does it play? Are there some other MNPs coated by the same copolymer or different copolymer reported? The author is suggested to enrich the "Introduction" or "Discussion" section, and this may highlight the significance and innovation of this work.

3. How is the stability of the polymer coated magnetic nanoparticles at different simulated physiological microenvironment, such as in bloodsteam (pH 7.4) or extracellular (pH 6.8 with H2O2) and intracellular (pH 5.0 with GSH) condition at tumor site? This was important for the following clinical application.

4. The size distribution of the magnetic nanoparticles was not some well, are there some other methods to improve the size distribution?

5. For organic and inorganic system, the author was suggested to provide the thermogracimetric analysis and elemental analysis data or some other test to prove the successful preparation of the polymer coated magnetic nanoparticles, but not just with the TEM and DLS results.

6. The MFH treatment were just carried out in vitro on cancer cell line level. It maybe of more convincing that the in vivo test and evaluation for cancer treatment are implemented on animal experimental model in the future.

Reviewer #2: In this manuscript, Chen and coworkers examined their polystyrene-sulfonic-acid- coated magnetic nanoparticles (PSS-MNPs) -induced magnetic fluid hyperthermia (MFH) on SK-Hep1 hepatocellular carcinoma (HCC) cells for lethal thermal effects with a self-made AMF system. I suggest acceptance of this manuscript after addressing the following comments.

1. All figures need to be 300dpi. 2. label details in figure S2. 3.what are effects of PSS-MNPs MFH on normal cells？

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Reviewer #1: No

Reviewer #2: No

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Extracellular and intracellular intermittent magnetic-fluid hyperthermia treatment of SK-Hep1 hepatocellular carcinoma cells based on magnetic nanoparticles coated with polystyrene sulfonic acid

PONE-D-20-26378R1

Dear Dr. Yao,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Yi Cao

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors may need to provide better images if needed.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have adequately addressed the reviewer's comments raised in the previous round and the reviewer think that this manuscript is now acceptable for publication without further revision.

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No