Dear Dr. 吴,

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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Kind regards,

Bing Xu, PhD

Academic Editor

PLOS ONE

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 [Major Research and Development Project of the Liaoning Provincial Department of Science and Technology,2024JH2/102500045.]. 

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Additional Editor Comments (if provided):

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: 1.It is recommended to supplement the encapsulation efficiency and drug loading data of nanoparticles.

2.Hemolysis test and plasma stability testing should be added.

3.It is suggested to set up a control group of free exosomes + free dBET6 to exclude the effect of simple physical mixing.

Reviewer #2: This manuscript describes the albumin nanoparticles conjugated with dBET6 and subsequently coated with exosomes to produce Exo-BSA@dBET6 hybrid nanoparticles. The authors conducted characterization studies, cellular uptake experiments, and antitumor activity assays, demonstrating that Exo-BSA@dBET6 exhibits superior cellular uptake and in vitro antitumor activity compared to free dBET6. They also explored its underlying mechanism. Although multiple experiments were performed, the results do not sufficiently support the authors’ claims. Therefore, I recommend major revision before acceptance in PLOS ONE.

1.The TEM image in Figure 1A is not consistent with Figure 1B. Is the “spherical vesicle structure” referring to the large dark feature in the center or the small aggregated dots in the background? If it is the latter, please provide a higher-magnification image to show the morphology more clearly.

2.In Figure 1C, the authors claim that “the nanoparticles have a molecular weight similar to that of BSA.” However, this is not clearly shown in the SDS-PAGE results, as the BSA lane appears incorrectly loaded.

3.The manuscript uses both “dbet6” and “dBET6.” Please confirm if they refer to the same compound and ensure consistent formatting throughout the text.

4.In Figure 2B, please label each panel clearly.

5.In Figure 3A, what is the unit of concentration used for the cytotoxicity assay? For the y-axis labeled “cell viability (%)” please verify that the scale correctly ranges from 0 to 100.

6.The claim of an “enhanced ability of Exo-BSA@dBET6 to promote tumor cell death” in Figure 3B is not convincingly supported. Please include quantitative analysis, such as live/dead cell counts or other relevant measurements, to substantiate this conclusion.

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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: Yes:  Jun Jiang

Reviewer #2: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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Attachments

Attachment

Submitted filename: General Assessment_Varamini.pdf

Exosome Encapsulated Albumin Nanoparticles Target Delivery of DBET6 as a Treatment for Triple-negative Breast Cancer

PONE-D-25-29407R1

Dear Dr. Wu,

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,

Bing Xu, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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

Reviewer #2: Yes

Reviewer #3: (No Response)

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

Reviewer #2: Yes

Reviewer #3: (No Response)

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

The PLOS Data policy

Reviewer #2: Yes

Reviewer #3: (No Response)

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

Reviewer #2: Yes

Reviewer #3: (No Response)

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Reviewer #2: (No Response)

Reviewer #3: (No Response)

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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 #2: No

Reviewer #3: No

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