Structural, Magnetic, and Magnetothermal Properties of Co_100−xNi_x Nanoparticles for Self-Controlled Hyperthermia

Round 1

Reviewer 1 Report

Title: Structural, magnetic, and magnetothermal properties of Co100-xNix nanoparticles for self-controlled hyperthermia

Authors: M. Hisham Al Nasir, Shumaila Siddique, Samson Aisida, Yasir Altowairqi, Mohammad Shariq, Mohammed M. Fadhali, M. Shakir Khan, Muhammad Azam Qamar, Tauseef Shahid

General Comments:

o  In this paper, series of a series of functionalized Co100-xNix (x = 20, 30, 40, 50, 60, 80, 85) nanoparticles were used as potential candidates for cancer treatment by hyperthermia. The structural, magnetic properties, and heating capacity of (NPs) is analyzed and discussed.

o   The structure of the article fulfills the structure of a research article.

o   Five keywords are included by the authors.

• The Introduction section provide sufficient background information for readers in the immediate field to understand the problem that this study addresses.

o   The authors present in the Experimental procedure section shortly the reagents, the experimental method and the equipment used.

o   In the Results and Discussion section, the authors present and interpret the results of the performed experiments.

o   The paper ends with the Conclusions part. In this section the authors mention the conclusions of their research study.

I suggest to Reconsider after Minor Revisions for the following reasons:

1. please rephrase the next sentences: page 1, lines 17-18; page 4, lines 145-146; page 11, lines 323-324 and 338-340;

2. page 12, line 358 – delete word “and”;

3. please used the same font throughout the text;

4. please note the alloy composition with subscripts (attention at page 3, lines – 93-110);

5. please use the superscript for m³, line 98;

6. please explain what TC means (or it is a typo and the authors refer to Curie temperature);

7. please correct the alloy composition at page 6, line 209

Author Response

Manuscript ID: Coatings-1808315

Title: Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia

Author: M. Hisham Al Nasir, Shumaila Siddique, Samson O. Aisida, Y. Altowairqi, Mohammad Shariq, Mohammed M. Fadhali, M. Shakir Khan, Muhammad Azam Qamar and Tauseef Shahid

Dear Editors and Referees:

Thank you for your kind letter of “Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia” on July 04, 2022. We revised the manuscript in accordance with referees’ and editor’s comments, and carefully proof-read the manuscript to minimize typographical, grammatical, and bibliographical errors. We sincerely hope this manuscript will be finally acceptable to be published in Coating Material Chemistry. Here below is our description in revision according to the comments.

REVIEWER REPORT:
Referee: 1

1. please rephrase the next sentences: page 1, lines 17-18; page 4, lines 145-146; page 11, lines 323-324 and 338-340;

Response:                                                                                                                   

Thanks for your kind suggestion. We have rephrased the sentences according to your advice.

2. page 12, line 358 – delete word “and”

Response:                                                                                                                   

Thanks for your kind suggestion. We have corrected it according to your advice.  

3. please used the same font throughout the text

Response:

Thanks for your kind suggestion. We carefully proofread the manuscript to minimize typographical, grammatical, and bibliographical errors.  

4. please note the alloy composition with subscripts (attention at page 3, lines – 93-110);

Response:

Thanks for your kind suggestion. We have corrected the composition throughout the manuscript.

5. please use the superscript for m3, line 98;

Response:

Thanks for your kind suggestion. We have corrected it according to your advice.  

6. please explain what TC means (or it is a typo and the authors refer to Curie temperature);

Response:

Thanks for your kind suggestion. It is Curie temperature T_C, we have corrected it according to your advice.

7. please correct the alloy composition at page 6, line 209

Response:

Thanks for your kind suggestion. We have corrected it according to your advice.

All the changes in the revised manuscript are highlighted in blue.
Thank you and all the referees for the kind advice.

Sincerely yours,
Dr M Hisham Alnasir

Reviewer 2 Report

An interesting work has been reported by Hisham Al Nasir et al., in which the structural, magnetic properties, and heating capacity of a cobalt-nickel nano-alloy coated by oleic acid (with the general formulation of Co_100-xNi_x) have been investigated. The focus of the report is made on saturation magnetization and tunable TC. The structural analyses have been performed, although this part is suffering from the lack of EDS and SEM energy-mapping analyses. It has been observed that a reduction in particle size leads to reduction of the TC value. Also, higher values of SAR and SLP have been estimated for the powder and fluid samples, which are larger than the maghemite, magnetite, and various mixed ferrites. The obtained results were well interpreted by the authors, and matched to each other in a good order. However, the lack of a nice graphical presentation of the preparation and synthetic routes is easily sensed. So, I would suggest the authors to add a nice scheme about that if it would be possible for them. Finally, I would recommend the editor to reconsider a revised version of the submitted manuscript, in which the following concerns are addressed;

1. The main content from abstract to conclusion needs an English polishing!

2. Authors are suggested to remove hyperthermia from Keywords section, as they mentioned this term in the title. It can be replaced with some other related words like “ferrofluids”.

3. In the first paragraph of the introduction section, authors are suggested to more discuss the importance of the magnetic particles in different field such as drug delivery, catalysis, photocatalysis, environmental science, energy conversion, and etc. In this regard, the authors should cite the pioneering work, as follows;

https://doi.org/10.1007/978-3-030-34007-0_32-1; https://doi.org/10.1016/j.ijbiomac.2022.01.028; https://doi.org/10.1002/psc.3277; https://doi.org/10.1007/s10934-022-01259-5; https://doi.org/10.1002/smll.202002733; https://doi.org/10.1039/D0NJ06022D; https://doi.org/10.1016/j.carres.2022.108632

4. Line 44, “106” or “10 to the power of 2”? Please check and correct.

5. Authors are suggested to refer to the important information about the challenges of hyperthermia in the clinicalization process. Is “Co_100-xNi_x” an appropriate candidate for real usage in the clinics? If yes, say the reasons in the context.

6. The lines 180-182 (XRD section) need to be supported by the appropriate references. Also, the lines 184-186, 187, 188, should be supported by the references.

7. In the same section, the authors state “One can also see from the results of XRD 196 measurements that the intensity of the BM85-100 peaks decreases with the increase of 197 milling time.”, but did not bring any reason for that! Please complete your interpretation by addition of the logical justifications.

8. For Figure 3, authors should refer to the curves’ origin! It has not been mentioned neither in the figure caption, nor in the context.

9. Readers need to see the EDX results (both qualification and quantification results) for the neat Co15N85 and oleic acid-coated Co₁₅N₈₅ MNPs. It would be appropriate for the clearance of the composition states.

10. SEM energy-mapping images should be provided for the samples. It would be appropriate for the clearance of the composition states.

10. The TGA curve is a bit strange! Usually, a partial increase in the weight is observed for this type of solid nano-sized samples due to the physical adsorption of the moisture onto the surfaces. Then, this weight gain is immediately lost through heating the sample up to around 110 ^oC. Could the authors please give a justification about disappearance of the mentioned weight gain in their case?

Finally, thanks to the authors for reporting such a nice work.

Comments for author File: Comments.docx

Author Response

Manuscript ID: Coatings-1808315

Title: Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia

Author: M. Hisham Al Nasir, Shumaila Siddique, Samson O. Aisida, Y. Altowairqi, Mohammad Shariq, Mohammed M. Fadhali, M. Shakir Khan, Muhammad Azam Qamar and Tauseef Shahid

Dear Editors and Referees:

Thank you for your kind letter of “Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia” on July 17, 2022. We revised the manuscript in accordance with referees’ and editor’s comments, and carefully proof-read the manuscript to minimize typographical, grammatical, and bibliographical errors. We sincerely hope this manuscript will be finally acceptable to be published in Coating Material Chemistry. Here below is our description in revision according to the comments.

REVIEWER REPORT:
Referee: 2

1. The main content from abstract to conclusion needs an English polishing!

Response:                                                                                                                   

Thanks for your kind suggestion. Thanks for your kind suggestion. We carefully proofread the manuscript to minimize typographical, grammatical, and bibliographical errors.

2. Authors are suggested to remove hyperthermia from Keywords section, as they mentioned this term in the title. It can be replaced with some other related words like “ferrofluids”.

Response:

Thanks for your kind suggestion. We have replaced the suggested word according to your advice.

3. I In the first paragraph of the introduction section, authors are suggested to more discuss the importance of the magnetic particles in different field such as drug delivery, catalysis, photocatalysis, environmental science, energy conversion, and In this regard, the authors should cite the pioneering work, as follows.

https://doi.org/10.1007/978-3-030-34007-0_32-1

https://doi.org/10.1016/j.ijbiomac.2022.01.028.

https://doi.org/10.1002/psc.3277;

https://doi.org/10.1007/s10934-022-01259-5;

https://doi.org/10.1002/smll.202002733;

https://doi.org/10.1039/D0NJ06022D;

https://doi.org/10.1016/j.carres.2022.108632.

Response:

Thanks for your kind suggestion. We have added the above references at their appropriate places.

4. Line 44, “106” or “10 to the power of 2”? Please check and correct.

Response:

Thanks for your kind suggestion. We have corrected it according to your advice.

5. Authors are suggested to refer to the important information about the challenges of hyperthermia in the clinicalization process. Is “Co_100-xNi_x” an appropriate candidate for real usage in the clinics? If yes, say the reasons in the context.

Response:

Thanks for your kind suggestion. Magnetic nanoparticles to be used for biomedical applications should be in the range of 10 ~ 100 nm [1, 2], which is considerably smaller than to the size of single blood cells (3.2 ~ 6.5 μm) and blood vessels (3 ~ 46 μm) [3]. They should be preferably spherical in shape to allow their smooth passage through biological systems [4]. For in vivo applications, must be stable, monodispersed, non-toxic, and biocompatible, which requires controlling particle size as well as the material and coating agents [5, 6]. Small-sized  have the following advantages:

1. They have good colloidal stability and resist aggregation.
2. They have weaker dipolar interactions, which minimizes particle aggregation             when the magnetic field is removed.
3. They can easily pass through the capillaries of organs and tissues, avoiding             vessel embolism.

The most commonly  in biomedical applications are mainly magnetite (Fe₃O₄), tetragonal maghemite (γ-Fе₂О_з) and hexagonal hematite (α-Fе₂О_з) [7, 8]. These  tend to destabilize and undergo to aggregation process in test media [9]. Therefore, it is necessary to stabilize the uncoated For to interact with biological systems, and they must have the ability to elude the reticuloendothelial system (). After injection of  into the bloodstream, they are rapidly coated with blood plasma proteins by a process known as opsonization. It has been shown that certain types of coatings, e.g., polyethylene glycol and derivatives of dextran, can allow the  to avoid opsonization, thereby increasing their circulation time in the bloodstream and enhancing their probability of reaching the targeted cells [10, 11].

Surface modification of  by coating with organic species (including surfactants or polymers) and inorganic layers (such as silica or carbon) can improve the ability of the  to elude the reticuloendothelial system () [12]. Coating with high molecular weight polymers increases the hydrodynamic size of the [13], which modifies their diffusional properties and biodistribution. The coating also plays an essential role in the colloidal stability of the against aggregation by reducing dipolar interactions [14, 15]. The most commonly studied coated materials are derivatives of polyvinyl amine () dextran and polyethylene glycol () [14, 15].

On the other hand, one of the limiting factors among the potential agents for magnetic hyperthermia is the risk of overheating, which can lead to spot heating and necrosis of healthy tissue. A direct approach to overcome this issue is to make the self-regulated. This can be accomplished by adjusting their Curie temperatures so that they lie in the therapeutic temperature of 315 to 320 K. When the temperature of the increases above , they lose their ferromagnetic properties and become paramagnetic, thereby losing their heating capability. Thus, the  act as self-regulating heat switches between ferromagnetic and paramagnetic states. This modality of potential cancer treatment, known as self-controlled magnetic hyperthermia,  can avoid the risks of spot heating, overheating and damage to healthy tissue.

Is “Co_100-xNi_x” an appropriate candidate for real usage in the clinics? If yes, say the reasons in the context.

Response:

To investigate the suitability of the developed MNP’s for actual biomedical applications, nanoparticles of some selected compositions were investigated for their cytotoxicity in terms of percentage of hemolysis. Hemolysis analysis was carried out on fresh human blood samples to study the toxicity of bare and oleic acid-coated nanoparticles. Oleic acid coated MNP’s significantly reduced toxicity of the MNP’s making them suitable candidates for biomedical applications such as self-controlled magnetic hyperthermia. Furthermore, liposome encapsulated Co_100-xNi_x nanoparticles for cytotoxicity in HeLa cell culture still in progress and would be followed by extended biocompatibility studies and in vitro and in vivo magnetothermal therapy experiments on cancer cells.

6. The lines 180-182 (XRD section) need to be supported by the appropriate references. Also, the lines 184-186, 187, 188, should be supported by the references.

Response:

Thanks for your kind suggestion. We have added the references at their appropriate places.

7. In the same section, the authors state “One can also see from the results of XRD 196 measurements that the intensity of the BM85-100 peaks decreases with the increase of 197 milling time.”,but did not bring any reason for that! Please complete your interpretation by addition of the logical justifications.

Response:

Thanks for your kind suggestion. We have added the sentence. The intensities of the XRD peaks of the milled samples decreased with increasing milling time. This was probably due to a reduction in crystallite size. Moreover, the lattice constant for the ball milled samples reduces within tolerable limit as shown in Fig. 3b). 

8. For Figure 3, authors should refer to the curves’ origin! It has not been mentioned neither in the figure caption, nor in the context.

Response:

Thanks for your kind suggestion. For different Ni concentrations, we have observed significant variation in structural and magnetic properties. For example, for lower Ni contents, a dendritic morphology of CoNi nanoparticles changes to submicron spheres and then to agglomerated quasi-spherical form for large Ni contents as shown in Figure 5. Also, from Fig. 3a) and Fig. Fig. 8a), there is a significant correlation between average crystallite size and coercivity in dependence of Ni content; the coercivity value decreases (increases) with decreasing (increasing) average crystallite size. Also, the lower (higher) values of coercivity corresponding to lower (higher) Ni content may be attributed to (a) the high magnetocrystalline anisotropy of the HCP phase [16] and (b) the shape anisotropy induced by the changing the morphology of the MNPs [17]. On the other hand, The coercivity enhancement may also be due to the surface oxidation of the Ni or Co NPs due to the exchange bias effect between the ferromagnetic Co or Ni and antiferromagnetic CoO or NiO [18], which is not observed in our samples and can be excluded.

Since all the samples have been prepared under identical conditions, the observed variation in the average crystallite size in Fig. 3a) can be attributed to the different rates of alloy formation for different Ni concentrations.

9. Readers need to see the EDX results (both qualification and quantification results) for the neat Co₁₅N₈₅ and oleic acid coated Co₁₅N₈₅ It would be appropriate for the clearance of the composition states.

Response:

Thanks for your kind suggestion. We always use EDX attached to FE-SEM for analysis. Currently FE-SEM is out of order. We performed the ICP analysis for pure Co₁₅N₈₅ NPs (Table 2) whose atomic percent are close to the initial stoichiometric contents of precursors.

10. SEM energy-mapping images should be provided for the samples. It would be appropriate for the clearance of the composition states.

Response:

Thanks for your kind suggestion. Currently FE-SEM is out of order.  Our group also working on polymer embedded Co₁₅N₈₅ nanoparticles for self-controlled magnetic hyperthermia and magnetic self-healing composites. Your comments regarding SEM energy-mapping images would be considered for the clearance of the composition states.

11. The TGA curve is a bit strange! Usually, a partial increase in the weight is observed for this type of solid nano-sized samples due to the physical adsorption of the moisture onto the surfaces. Then, this weight gain is immediately lost through heating the sample up to around 110 ^o Could the authors please give a justification about disappearance of the mentioned weight gain in their case?

Response:

Thanks for your kind suggestion. We agree with reviewer comments. Since milling was done for 500 min. in the presence of oleic acid and heptane in the presence of an inert atmosphere. All the obtained samples were dried at 40 ^oC for 4 h and preserved in an inert gas container. During XRD analysis, we didn’t observe any oxide peak of NiO and CoO in our samples leading to the purity of the samples. Disappearing of the weight loss around 110 ^oC cannot be ignored but the presence of oleic acid layer on the MNPs surface and purity of the MNPs can lead to the weight loss in the temperature range of 50 – 380 ^oC.

All the changes in the revised manuscript are highlighted with blue.
Thank you and all the referees for the kind advice.
Sincerely yours,
Dr M Hisham Alnasir

References

1. Berry, C.C. and A.S.J.J.o.p.D.A.p. Curtis, Functionalisation of magnetic nanoparticles for applications in biomedicine. 2003. 36(13): p. R198.
2. Davis, M.E., Z. Chen, and D.M. Shin, Nanoparticle therapeutics: an emerging treatment modality for cancer, in Nanoscience and technology: A collection of reviews from nature journals. 2010, World Scientific. p. 239-250.
3. Joseph, A., A. Guevara-Torres, and J. Schallek, Imaging single-cell blood flow in the smallest to largest vessels in the living retina. Elife, 2019. 8: p. e45077.
4. Kolhatkar, A.G., et al., Tuning the magnetic properties of nanoparticles. Int J Mol Sci, 2013. 14(8): p. 15977-6009.
5. Bulte, J.W. and D.L. Kraitchman, Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed, 2004. 17(7): p. 484-99.
6. Nafee, N., et al., Relevance of the colloidal stability of chitosan/PLGA nanoparticles on their cytotoxicity profile. 2009. 381(2): p. 130-139.
7. Frankel, R.B., R.P. Blakemore, and R.S. Wolfe, Magnetite in freshwater magnetotactic bacteria. Science, 1979. 203(4387): p. 1355-6.
8. Mann, S., Structure, morphology, and crystal growth of bacterial magnetite, in Magnetite biomineralization and magnetoreception in organisms. 1985, Springer. p. 311-332.
9. Yu, S.-M., A. Laromaine, and A.J.J.o.n.r. Roig, Enhanced stability of superparamagnetic iron oxide nanoparticles in biological media using a pH adjusted-BSA adsorption protocol. 2014. 16(7): p. 2484.
10. Owens III, D.E. and N.A.J.I.j.o.p. Peppas, Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. 2006. 307(1): p. 93-102.
11. Roberts, M.J., M.D. Bentley, and J.M. Harris, Chemistry for peptide and protein PEGylation. Adv Drug Deliv Rev, 2002. 54(4): p. 459-76.
12. Shenoy, D.B. and M.M. Amiji, Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer. Int J Pharm, 2005. 293(1-2): p. 261-70.
13. Zaitsev, V.S., et al., Physical and chemical properties of magnetite and magnetite-polymer nanoparticles and their colloidal dispersions. 1999. 212(1): p. 49-57.
14. Orive, G., et al., Biomaterial-based technologies for brain anti-cancer therapeutics and imaging. Biochim Biophys Acta, 2010. 1806(1): p. 96-107.
15. Kateb, B., et al., Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? 2011. 54: p. S106-S124.
16. Hui, S., et al., Synthesis and characterization of structure controlled nano-cobalt particles. MRS Online Proceedings Library (OPL), 2002. 755.
17. Nie, D., et al., Chain-like CoNi alloy microstructures fabricated by a PVP-assisted solvothermal process. Materials Letters, 2014. 131: p. 306-309.
18. Nogués, J. and I.K. Schuller, Exchange bias. Journal of Magnetism and Magnetic Materials, 1999. 192(2): p. 203-232.

Reviewer 3 Report

The authors have studied the structural, magnetic properties, and heating capacity of a series of function-17 alized Co100-xNix (x = 20, 30, 40, 50, 60, 80, 85) nanoparticles (NPs). I will recommend publication after the authors will perform a minor revision of their manuscript. The following points should be addressed by the authors, before the manuscript may be reconsidered for publication:

1- The clarity of the manuscript comes through because of the simplicity of the results, but there are a large number of grammatical mistakes that need to be corrected. Please read through the text more carefully and correct the grammatical mistakes.

2-Are these compounds stable in the present form? 

3-Author should explain the clear impact of phase changing on physical properties.

4- Some related references that studied the structural and magnetic properties should be cited in the introduction section, such as: Materials Research Bulletin, 2018, 98, pp. 335–339; Journal of Magnetism and Magnetic Materials, 2019, 481, pp. 72–76; Journal of Superconductivity and Novel Magnetism, 2020, 33(5), pp. 1369–1375; Journal of Alloys and Compounds, 2018, 741, pp. 1196–1202.

Author Response

Manuscript ID: Coatings-1808315

Title: Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia

Author: M. Hisham Al Nasir, Shumaila Siddique, Samson O. Aisida, Y. Altowairqi, Mohammad Shariq, Mohammed M. Fadhali, M. Shakir Khan, Muhammad Azam Qamar and Tauseef Shahid

Dear Editors and Referees:

Thank you for your kind letter of “Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia” on July 13, 2022. We revised the manuscript in accordance with referees’ and editor’s comments, and carefully proofread the manuscript to minimize typographical, grammatical, and bibliographical errors. We sincerely hope this manuscript will be finally acceptable to be published in Coating Material Chemistry. Here below is our description in revision according to the comments.

REVIEWER REPORT:
Referee: 3

1. The clarity of the manuscript comes through because of the simplicity of the results, but there are a large number of grammatical mistakes that need to be corrected. Please read through the text more carefully and correct the grammatical mistakes.

Response:

Thanks for your kind suggestion. We carefully proofread the manuscript to minimize typographical, grammatical, and bibliographical errors. 

2. Are these compounds stable in the present form?

Response:

Yes. Co₁₅Ni₈₅ nanoparticles ball milled at 1425 rpm for 1000 and 1200 min. shows stable suspensions for 03 and 05 min respectively after stirring for 5 h.

3. Author should explain the clear impact of phase changing on physical properties.

Response:

Thanks for your kind suggestion. For different Ni concentrations, we have observed significant variation in structural and magnetic properties. For example, for lower Ni contents, a dendritic morphology of CoNi nanoparticles changes to submicron spheres and then to agglomerated quasi-spherical form for large Ni contents as shown in Figure 5. Also, from Fig. 3a) and Fig. Fig. 8a), there is a significant correlation between average crystallite size and coercivity in dependence of Ni content; the coercivity value decreases (increases) with decreasing (increasing) average crystallite size. Also, the lower (higher) values of coercivity corresponding to lower (higher) Ni content may be attributed to (a) the high magnetocrystalline anisotropy of the HCP phase [1] and (b) the shape anisotropy induced by the Changing the morphology of the MNPs [2]. On the other hand, The coercivity enhancement may also be due to the surface oxidation of the Ni or Co NPs due to the exchange bias effect between the ferromagnetic Co or Ni and antiferromagnetic CoO or NiO [3], which is not observed in our samples and can be excluded.

4. Some related references that studied the structural and magnetic properties should be cited in the introduction section, such as: Materials Research Bulletin, 2018, 98, pp. 335–339; Journal of Magnetism and Magnetic Materials, 2019, 481, pp. 72–76; Journal of Superconductivity and Novel Magnetism, 2020, 33(5), pp. 1369–1375; Journal of Alloys and Compounds, 2018, 741, pp. 1196–1202.

Response:

Thanks for your kind suggestion. We have added the above references.

All the changes in the revised manuscript are highlighted with blue.
Thank you and all the referees for the kind advice.
Sincerely yours,
Dr M Hisham Alnasir

References

1. Hui, S., et al., Synthesis and characterization of structure controlled nano-cobalt particles. MRS Online Proceedings Library (OPL), 2002. 755.
2. Nie, D., et al., Chain-like CoNi alloy microstructures fabricated by a PVP-assisted solvothermal process. Materials Letters, 2014. 131: p. 306-309.
3. Nogués, J. and I.K. Schuller, Exchange bias. Journal of Magnetism and Magnetic Materials, 1999. 192(2): p. 203-232.

Reviewer 4 Report

The work presented by Al Nasir et.al, deals with the structural and magnetic characterization of oleic acid-coated Co100-xNi NPs synthesized by the hydrothermal method and subsequent ball milling. In addition, the work focuses on the study of the magnetic hyperthermia performance of samples as a function of several factors such as the magnetic AC applied, particle size, and composition. The main result of this study is the capacity to tune the magnetic properties of samples by just monitoring the Ni composition.  I found this work interesting and valuable for the research community, but the main message is not clear and some of the parts are difficult to understand. So, I suggest revising some of the parts of the manuscript such as the abstract, the introduction, and the conclusions to enhance the quality of the final work. Apart from that, I've found some typos and general questions or suggestions in the document that I suggest revising.

1)     I suggest uniforming the manner to describe nanoparticles/NPs.

2)     Extra spaces are detected in several captions of Table 1, Figures 5, 6, and 8, among others.

3)     I did not find an explanation of the effect of oleic acid on the particle surface for the hemolysis activities of samples on the section results and discussions.

4)     I recommend adding a short paragraph in the conclusion detailing the potential use of these NPs in medical treatment and in other fields such as magnetic self-healing composites.

Author Response

Manuscript ID: Coatings-1808315

Title: Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia

Author: M. Hisham Al Nasir, Shumaila Siddique, Samson O. Aisida, Y. Altowairqi, Mohammad Shariq, Mohammed M. Fadhali, M. Shakir Khan, Muhammad Azam Qamar and Tauseef Shahid

Dear Editors and Referees:

Thank you for your kind letter of “Structural, magnetic, and magnetothermal properties of Co_100-xNi_x nanoparticles for self-controlled hyperthermia” on July 17, 2022. We revised the manuscript in accordance with referees’ and editor’s comments, and carefully proof-read the manuscript to minimize typographical, grammatical, and bibliographical errors. We sincerely hope this manuscript will be finally acceptable to be published on Coating Material Chemistry. Here below is our description in revision according to the comments.

REVIEWER REPORT:
Referee: 4

1. I suggest uniforming the manner to describe nanoparticles/NPs.

Response:                                                                                                                   

Thanks for your kind suggestion. We have corrected it according to your advice.

2. Extra spaces are detected in several captions of Table 1, Figures 5, 6, and 8, among others.

Response:

Thanks for your kind suggestion. We have corrected it according to your advice.

3. I did not find an explanation of the effect of oleic acid on the particle surface for the hemolysis activities of samples in the section results and discussions.

Response:

Thanks for your kind suggestion. We have added the following paragraph to the manuscript.

“Possible cytotoxicity of Co₁₅Ni₈₅ NPs ball milled for 100, 200, 300 and 500 min at 1425 rpm was estimated by preparing 100 µg/ml of MNPs in chloroform. The degree to which the MNPs cause damage to red blood cells (RBCs), was studied in terms of haemolysis [1]. MNPs interacting with RBCs can damage the cell membrane and interact with the hemoglobin, causing its structural and conformational changes [2]. The higher percentage of haemolysis indicates higher cytotoxicity of the MNPs [3]. Results for cytotoxicity assay in the form of percentage haemolysis for oleic acid coated and uncoated Co₁₅Ni₈₅ MNPs are shown in Table 1, it has been shown by Purohit et al. [4] that coating gold nanoparticles with bovine serum albumin reduce the haemolysis effect. Also, oleic acid is a well-known biocompatible material [5, 6]. In our case, oleic acid-coated MNPs show a significant reduction in the percentage of haemolysis by reducing direct contact of MNPs with the surface of the RBCs. Therefore, oleic acid coated Co₁₅Ni₈₅ MNPs showed significantly lower haemolysis at similar concentrations, suggesting that these MNPs could be of great importance in biomedical applications such as self-controlled magnetic hyperthermia.”

4. I recommend adding a short paragraph in the conclusion detailing the potential use of these NPs in medical treatment and in other fields such as magnetic self-healing composites.

Response:

Thanks for your kind suggestion. We have added the following sentences to the manuscript.

“MRI contrast agent, drug delivery, magnetic bio detection, magnetic self-healing composites, nanoparticle-based biosensors and other biomedical applications.”

All the changes in the revised manuscript are highlighted with blue.
Thank you and all the referees for the kind advice.
Sincerely yours,
Dr M Hisham Alnasir

References

1. Barshtein, G., D. Arbell, and S. Yedgar, Hemolytic effect of polymeric nanoparticles: role of albumin. IEEE Transactions on NanoBioscience, 2011. 10(4): p. 259-261.
2. Groopman, J.E. and L.M. Itri, Chemotherapy-induced anemia in adults: incidence and treatment. Journal of the National Cancer Institute, 1999. 91(19): p. 1616-1634.
3. Mocan, T., Hemolysis as expression of nanoparticles-induced cytotoxicity in red blood cells. BMBN, 2013. 1(1): p. 7-12.
4. Purohit, R., et al., Effect of gold nanoparticle size and surface coating on human red blood cells. Bioinspired, Biomimetic and Nanobiomaterials, 2016. 5(3): p. 121-131.
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Round 2

Reviewer 2 Report

Thanks for improving the manuscript.

Reviewer 4 Report

The article is now fine to be published. Congrats!