Synthesis of Chitosan-Coated Co0.5Zn0.5Fe2O4 Nanoparticles for Contrast Enhancement in Magnetic Resonance Imaging
Round 1
Reviewer 1 Report
The authors must make serious efforts to improve their work. A lot of errors are present in their paper, starting with a poor English language and ending with the scientific presentation of their data.
It is not clear if parts of their studies is based on original methods or based on previously described methods (for instance, the synthesis of NPs, the method of coating, etc.).
No information is provided on the source and quality of the materials used.
Confusion of species in animal experiments - Wistar rats or mice (as later mentioned in the paper). No description of the lab condition for the animals.
The authors claim "lack of acute toxicity", but except of the evolution of weight no other data were provided.
Author Response
Dear Reviewers,
I revised the manuscript as suggested by reviewers and sent English proof from the MDPI service. Please see the attachment.
Best Regards,
Apichaya Worawong (KMUTT)
Author Response File: 
Author Response.docx
Reviewer 2 Report
The study presented in this research is sound, and the results produced are interesting. But a revision is required, and after responding to the following remarks and revising the paper, the manuscript may be considered for publication.
1. Literature review needs to include several recent, relevant publications (high impact) highlighting their key findings. The current version only discussed general aspects while the review of each from several papers is necessary. You may provide a review summary table consisting of a column for the comments or key conclusions.
2. More recent relevant literature or similar work discussion is mandatory in the introduction section, which is missing in the Introduction. Authors are suggested to add one paragraph in the introduction section by discussing the recent progress and citing similar work.
3. The novelty of the work is missing in the introduction. Authors are suggested to include a separate paragraph discussing the novelty and importance of the present work.
4. Authors are suggested to include a literature review on the recent publication of the following references in the introduction section: DOIs: 10.1016/j.rinp.2018.06.010; 10.1016/B978-0-12-824272-8.00009-9; 10.1016/j.apmt.2021.101104; 10.1201/9781003197492-10; 10.1016/B978-0-12-823688-8.00002-8.
5. Also, check the typos throughout the manuscript during revision submission.
Author Response
Dear Reviewers,
I revised the manuscript as suggested by reviewers and sent English proof from the MDPI service. Please see the attachment.
Best Regards,
Apichaya Worawong (KMUTT)
Author Response File: Author Response.docx
Reviewer 3 Report
2.1. Synthesis of Chitosan-coated Co0.5Zn0.5Fe2O4 Cobalt–zinc ferrite (Co0.5Zn0.5Fe2O4) nanoparticles were synthesized by co-precipitation method mixed with cobalt (II) nitrate (Co(NO3)2·6H2O), zinc (II) nitrate (Zn(NO3)2·6H2O) and iron(III) nitrate (Fe(NO3)3·9H2O), Did they co-precipitated by reacting with each other or added any solvents to make them precipitate, mention clear procedure of preparation? Chitosan-coated Co0.5Zn0.5Fe2O4 nanoparticle was prepared by adding 2 % of chitosan with 1 % of acetic acid, how much total volume of solvent was taken?
2.3. Biocompatibility, why only female wistar rats were used for this study, since prepared material can be used for both male and female? Authors must Mention the animal approval number in the manuscript.
2.4. Animal testing, what is the difference between mouse and rat? Authors mention both terminology in this, why?
Figure 3. TEM images of chitosan-coated Co0.5Zn0.5Fe2O4 nanoparticles with the external magnetic field assistance of 400 mT, figure 3a inside the histogram picture is not clear, please revise it.
Figure 4. FTIR spectra of chitosan-coated Co1-xZnxFe2O4 with x=0.1, 0.5, 0.9 nanoparticles at calcine temperature 500 ๐C, why was not performed FTIR of physical mixture of all components and individual? it is necessary to check the interaction between components without magnetic field. Add it into revised manuscript.
Figure 6. The body weight changes of Wistar rats in acute systemic toxicity with chitosan-coated
Co0.5Zn0.5Fe2O4 nanoparticles. Why is the difference in body weight between two injection of chitosan coated nanoparticles, one group is losing weight and one is gaining weight as compared to normal saline control? Where is the gadolinium group results? Why statistical analysis was not performed to check the difference between groups body weight?
Author Response
Dear Reviewers,
I revised the manuscript as suggested by reviewers and sent English proof from the MDPI service. Please see the attachment.
Best Regards,
Apichaya Worawong (KMUTT)
Author Response File: Author Response.docx
Reviewer 4 Report
This manuscript is a very interesting and detailed description of chitosan-coated Co0.5Zn0.5Fe2O4 nanoparticles prepared by External Magnetic Field that can be used as contrast agent in MRI. This is an up-to-date and challenging area of research which is worth dealing with.
In general, the manuscript is well drafted understandable. The Figures and Tables are all clear and they support the text in manuscript. The characterizations and measurements, such as XRD, FT-IR, and the biocompatibility studies are described well and satisfactorily evaluated.
Moreover, it is particularly interesting, unique, and commendable that there are in vivo/aminal tests included. The description and discussion of MRI application is very detailed and clear.
In my opinion, this manuscript is worthy of publication as is.
Author Response
Dear Reviewers,
Thank you very much for your review and appreciation of our research. I revised the manuscript as suggested by reviewers and sent English proof from the MDPI service.
Best Regards,
Apichaya Worawong (KMUTT)
Round 2
Reviewer 1 Report
Dear authors,
even the present, revised paper, is far from the standard of a scientific publication. As far as I am concerned, even if you tried to clarify the aspects regarding the animal experiments, the experiments do not seem to comply to the required rules of admitting the study.
Author Response
Dear reviewer,
I am very grateful for the reviewer's suggestions. I have revised the manuscript at the suggestion of all reviewers and corrected the English by submitting the MDPI English service. Moreover, prior to the MRI testing of the mice, I completed training in animal testing, including acute toxicity testing, and consulted with veterinarians and animal care practitioners, as well as clinical diagnosticians. MRI machines are used by others studies in animal studies as well.
Please see the attachment
Best regards,
Apichaya Worawong (KMUTT)
Author Response File: 
Author Response.pdf
