Synthesis and Characterization of Core–Shell Magnetic Nanoparticles NiFe₂O₄@Au

Round 1

Reviewer 1 Report

Additional characterization could be added to ensure the integrity of the gold shell i.e. not broken shell. For example:

K Tschulik, K Ngamchuea, C Ziegler, MG Beier, C Damm, A Eychmueller, RG Compton, Advanced Functional Materials, 25 (32), 5149-5158

Author Response

We are thankful to Reviewer for their careful work of the manuscript, and their constructive comments. We agree that additional characterization the integrity of the gold shell could be useful. Your suggestion about electrochemical differentiation solid and cracked or broken core–shell NPs is very interesting and valuable. Unfortunately, we do not have such equipment in the moment. However, we have read the paper K Tschulik, K Ngamchuea, C Ziegler, MG Beier, C Damm, A Eychmueller, RG Compton, Advanced Functional Materials, 25 (32), 5149-5158  and will keep in mind this method. We have added the paper to ‘References’.

Reviewer 2 Report

This manuscript reports a two-step synthesis of core-shell nanoparticles with a nickel ferrite core and a gold shell (NiFe2O4@Au), of interest for hyperthermia applications.

 

The first step consists in the synthesis of the NiFe2O4 NPs. This step seems successful. The XRD pattern displays the reflections expected from NiFe2O4 crystals. The synthesized NPs are also clearly observed in the bright field TEM image in figure 1 and the associated SAED pattern provides evidence for the suitable structural phase.

The second step is the deposition of a gold shell on the magnetic NPs through gold reduction from HAuCl4. The displayed results provide evidence for the presence of gold but in my view, the way the gold atoms are distributed on the magnetic NPs remains to be demonstrated. Clearly, I did not find in the paper any  evidence for the existence of the claimed 120 nm large NiFeO4@Au NPs, not even of 120 nm large NPs or of the presence of a gold shell surrounding the NPs. I thus cannot recommend this paper for publication.

 

Formal comments and questions

• In the title, the authors wrote “Au@NiFe2O4”, which is the reverse chemical order.
• The authors should explain why the NPs observed in TEM (fi 1) are much larger than the size deduced from XRD. Does this means that a NP contains several crystallites, or is it partially disordered?
• The observed NPs in figure 1 seem faceted (flat facets are clearly distinguished) and not spherical, as written.
• Fig 3a shows the presence of small NPs, probably gold NPs. If they were distributed randomly all over the surface of the nickel ferrite NPs (to form progressively a shell), we should see them by transparency on the magnetic NPs as they would appear much darker owing to amplitude contrast (Au is metallic and heavy). On the contrary, the gold NPs seem to be embedded in a kind of film, sometimes surrounding a NP.
• In its present form, nothing can be said about figure 3b and certainly not that we observe 120 nm core-shell NPs. If they do have this evidence, the authors should present it here.
• The fact that both kinds of NPs, nickel ferrite and gold ones, are present is not a proof of the formation of core-shell.
• The caption of figure 5 is lacking
• XPS spectra essentially show the presence of gold and not only metallic gold. But again, this result is not an evidence for the presence of a gold shell around the magnetic NPs. The gold NPs can form a sort of films embedding the magnetic NPs like a thick matrix.
• This would still be a composited film but not formed of core-shell NPs.

Comments for author File: Comments.pdf

Author Response

Reply: We are thankful to Reviewer for their careful reading of the manuscript, the criticism, and their constructive comments which allow us to improve the paper. Please find below a detailed point-by-point response to all comments (reviewers’ comments in black, our replies in blue).

This manuscript reports a two-step synthesis of core-shell nanoparticles with a nickel ferrite core and a gold shell (NiFe204@Au), of interest for hyperthermia applications.

The first step consists in the synthesis of the NiFe204 NPs. This step seems successful. The XRD pattern displays the reflections expected from NiFe204 crystals. The synthesized NPs are also clearly observed in the bright field ТЕМ image in figure 1 and the associated SAED pattern provides evidence for the suitable structural phase.

The second step is the deposition of a gold shell on the magnetic NPs through gold reduction from HAuC₁₄. The displayed results provide evidence for the presence of gold but in my view, the way the gold atoms are distributed on the magnetic NPs remains to be demonstrated. Clearly, I did not find in the paper any evidence for the existence of the claimed 120 nm large NiFe04@Au NPs, not even of 120 nm large NPs or of the presence of a gold shell surrounding the NPs. I thus cannot recommend this paper for publication.

Formal comments and questions

• In the title, the authors wrote "Au@NiFe204", which is the reverse chemical order.

Reply: Thank You, we have corrected that.

• The authors should explain why the NPs observed in ТЕМ (fi 1) are much larger than the size deduced from XRD. Does this means that a NP contains several crystallites, or is it partially disordered?

Reply: We apologize for the technical mistake. We have recalculated average NiFe₂O₄ nanoparticles crystalline size from the peak broadening for the four most intensive powder XRD peaks (<30.33>; <35,73>; <43,43>; <57,45>) and it was 24,8±2,6 nm. We have corrected that.

• The observed NPs in figure 1 seem faceted (flat facets are clearly distinguished) and not spherical, as written.

Reply: Thank You, we have corrected that.

• Fig 3 a shows the presence of small NPs, probably gold NPs. If they were distributed randomly all over the surface of the nickel ferrite NPs (to form progressively a shell), we should see them by transparency on the magnetic NPs as they would appear much darker owing to amplitude contrast (Au is metallic and heavy). On the contrary, the gold NPs seem to be embedded in a kind of film, sometimes surrounding a NP.

Reply: Fig 3a shows the result of a single gold coating, the surface of magnetic particles is inlaid with gold seeds (2-3 nm), which are darker than  nickel ferrite NPs. That is, in the first gold deposition step NPs decorated with Au⁰ are formed. The small gold seeds significantly increase in size during the second step and form the continuous gold shell during the third stage. We calculate average nanoparticle crystalline size using the Scherrer equation from XRD patterns of NiFe₂O₄@Au NPs after two-stage and three-stage gold deposition (Figure 4). Moreover, the XRD peaks of NiFe₂O₄ phase (<30.33>; <35,73>; <57,45>) and XRD peak of Au⁰ phase  (<38.1>) were used for the calculation separately. The average nanoparticle crystalline size determined for the peaks of NiFe₂O₄ phase for both samples (after two-stage and three-stage coating) was 25,2±2,0 nm, which corresponds to the NiFe₂O₄ particle size before coating. At the same time, the NPs size determined for the peaks of gold phase was 23,5 нм (two-stage coating) and 25,5 (three-stage coating). These findings confirm that the gold shell covers several nickel ferrite crystals, which size do not change in the gold deposition process. However, small gold seeds obtained in the first coating step significantly increase in size during the second step and form the continuous gold shell during the third stage.

• In its present form, nothing can be said about figure 3b and certainly not that we observe 120 nm core-shell NPs. If they do have this evidence, the authors should present it here.

Reply: We have added electron diffraction patterns of hybrid NiFe₂O₄@Au NPs after one-stage and three-stage methionine-directed gold deposition. In the first case we can see  diffraction rings corresponding to both nickel ferrite and gold, however at the second case diffraction rings of gold are only observed in the electron microdiffraction pattern due to a continuous gold shell.

• The fact that both kinds of NPs, nickel ferrite and gold ones, are present is not a proof of the formation of core-shell.

Reply: XRD analysis has the more resolution in depth, as a result reflexes of both phases nickel ferrite and gold are observed in the XRD pattern. The no rings of nickel ferrite phase are observed in the electron diffraction patterns (TEM) because NiFe2O4 is covered by thick layer of gold, i.e. Au shell.

• The caption of figure 5 is lacking

Reply: Thank You, we have corrected that.

• XPS spectra essentially show the presence of gold and not only metallic gold. But again, this result is not an evidence for the presence of a gold shell around the magnetic NPs. The gold NPs can form a sort of films embedding the magnetic NPs like a thick matrix. This would still be a composited film but not formed of core-shell NPs.

Reply: If gold forms a matrix with embedded the magnetic NPs XPS spectra show the presence of nickel and iron too. We do not claim that particles with a single crystal core are formed. Gold coating is most likely not a single-layer and covers several nickel ferrite crystallites.

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Please see attached file for comments and suggestions for authors

Comments for author File: Comments.pdf

Author Response

Reply: We are grateful to the reviewer for a thorough review and for posing many important questions. We have tried to respond to each question/statement and have also edited the revised manuscript. Please find below a detailed point-by-point response to all comments (reviewers’ comments in black, our replies in blue).

1. There are several typos in the text that should be corrected, for example "NPs" or "Nps".

Reply: Thank You, we have corrected that.

2. In part 3.1 : It would be interesting to deepen the XRD study by showing the diffractogram of the Nickel ferrite nanoparticles before and after annealing at 360°C.

Reply: We annealed our samples at 650 °C. The thermal analysis shows that crystallization of the product occurs at 605 °C. If the product was heated before this temperature it was not crystallized. For example, XRD pattern of the precursor of the nickel ferrite nanoparticles after annealing at 400 °C:

 

 

 

 

 

 

3. In part 3.2: The reduction mechanism of gold on the ferrite particles must be completed. It is not clear how Au(l) formed with thiol further reacts to give Au(lll) and Au(0).

Reply: Even though lots of research has been done the chemical mechanism of methionine oxidation by [AuCl₄]^- ions is still not understood. According to the literature data, reaction mechanism takes place in a few steps. The first step is a very fast coordination of methionine (Met) to the Au(III) ion. Met acts as bidentate S- and N-donor ligand and displaces the chloride anion in [AuCl₄]^- forming intermediate complex [AuCl₂(HMet)]²⁺ (in acidic solutions) or [AuCl₂(Met)]⁺ (in alkaline solutions). Several authors maintain that Au(III) ion coordinates only to the thioether sulfur and forms [AuCl₃(HMet)]⁺. At the second stage the reduction of Met takes place: the intermediate product reacts with second methionine molecule to generate Met sulfoxide as the product of the redox process. As result [AuCl₂]⁻ complex is formed. And finally [AuCl₂]⁻ disproportions forming [AuCl₄]− and metallic gold:

3[AuCl₂]^- = 2Au⁰ + [AuCl₄]^- +2Cl^-.

In [1] it was found that it was not possible to detect [AuCl₂]⁻ complex, due to its fast disproportionation in aqueous solution. Thus, to promote the reduction of gold(III) to gold(I) two methionine molecules are required.

We have added relevant explanations to the manuscript.

[1] B.Glišić, M. Djuran, Z. Stanić, S. Rajković Published Oxidation of methionine residue in Gly-Met dipeptide induced by [Au(en)Cl2]+ and influence of the chelated ligand on the rate of this redox process / Gold Bull (2014) 47:33–40.

4. UV Vis study must be completed with spectra of the Nickel ferrite particles before, after 4 hours and after several gold deposition's steps.

Reply: We have added the spectrum of the nickel ferrite nanoparticles before gold coating to Figure 2.  

5. It would be interesting to complete the study with DLS measurement of the core shell particles at various steps of gold coverage.

Reply: We had intention to determine particle size by DLS technique before the Covid-19 pandemic. Unfortunately, in Russia lockdown restrictions are not over yet. This study will be the aim of our future paper.

6. In Fig 3, (a) and (b) are missing on the pictures.

Thank you, we have corrected that.

7. Finally, the overall paper concerns magnetic nanoparticles, no studies on the magnetic properties are shown. The paper would certainly gain in interest if magnetic studies of the particles before and after gold coverage were shown.

Reply: We have added study on magnetic properties of  NiFe₂O₄  and NiFe₂O₄@Au NPs to the manuscript.

Author Response File: Author Response.pdf

Reviewer 4 Report

The comments are presented in the attachment.

Comments for author File: Comments.pdf

Author Response

Reply: We are grateful to the reviewer for a thorough review and for posing many important questions. We have tried to respond to each question/statement and have also edited the revised manuscript. Please find below a detailed point-by-point response to all comments (reviewers’ comments in black, our replies in blue).

Specific comments:

1. In the title, Au@NiFe₂O₄ NPs are formed and studied whereas in the main text - NiFe₂O₄@Au. Please correct the title because the shell is gold.

Reply: Thank you, we have changed the title.

2. In the 'Abstract' part it is reported that the hybrid NPs synthesized in this study can be applied for magnetic resonance imaging, hyperthermia and so on. However, any experimental verifications of these statements are presented in the paper. Also, 'magnetic hyperthermia' and 'cancer' words should be rejected from the paper 'Keywords'.

Reply: Unfortunately, we do not have experimental verifications of the application of obtained hybrid NPs for magnetic resonance imaging or hyperthermia. This study focuses on the synthesis of hybrid nanoparticles based on nickel ferrite nanoparticles and gold and the characterization of the products. The ‘Abstract’ has been revised and keywords have been changed.

3. According to the 'Materials and Methods' part, the synthesis of Ni ferrite NPs was conducted during 5 min whereas in the 'Results' part this procedure lasted 2 h. Please correct.

Reply: Thank you, we have corrected that.

4. In the 'Experimental' part the way by which the size distribution histogram was determined should be presented since ТЕМ image (Fig. lc) demonstrated highly agglomerated particles.

Reply: We have added this information to the manuscript.

5. From the XRD patterns the peaks, indicating the size of gold-coated magnetic NPs obtained by single deposition step, differ insignificantly from ones coated by three steps but the content of deposited gold and the final size of NPs differ drastically. Please explain.

Reply: Thank you for your comment. It is a technical mistake. Figure 4 shows XRD patterns of gold-coated magnetic NPs obtained by two and three steps of the gold deposition. The electron diffraction pattern of NPs after single-step deposition is shown in the Fig. 3b. Relevant explanations have added to the manuscript.

 

6. In the 'Conclusions' part, it is stated that "We propose a method that uses amino acid methionine as a reducer of gold species and stabilizing agent for NPs. However, this method has been presented clearly in the manuscript published by other scientists in J. Phys. Chem. 2015, 119, 117398. Please correct statement.

Reply: Thank you, we have revised the 'Conclusions' part and have added the reference to Experimental part.

7. The caption for Figure 5 is required.

Reply: Thank you, we have corrected that.

8. Please change 'u' (line 227, p.7) to 'and'.

Reply: Thank you, we have corrected that.

Author Response File: Author Response.pdf

Reviewer 5 Report

Please find the attached file for the comments. 

Comments for author File: Comments.pdf

Author Response

Reply: We are thankful to Reviewer for their careful reading of the manuscript and their constructive comments which allow us to improve the paper. Please find below a detailed point-by-point response to all comments (reviewers’ comments in black, our replies in blue).

1. Line 45: NiFe204 needs to rewrite properly with 2 and 4 in the subscript.

Reply: Thank you, we have corrected that.

2. I would suggest authors to use decimal instead of comma which seems confusing to readers. For example, in line 98, authors have used 0,1 mol/L which can be written as 0.1 mol/L.

Reply: Thank you, we have corrected that.

3. Line 162-168: First, I would ask authors to replace the y-axis to "Extinction" because the intensity is the sum of absorption and scattering. Authors compared the sample 2 with sample 1 and claimed that the reduction of chloroauric acid is taking place on the surface of nickel ferrite nanoparticles. Can you please also include the UV-Visible spectra of nickel ferrite nanoparticle for comparison? That will further support your statement. Which might also explain why there is shoulder in the UV-Visible spectrum at lower wavelength region. Another important question is how the chloroauric acid can get deposited on the surface of nickel ferrite. The authors need to provide some literature or supporting evidence if available.

Reply: We have replaced the y-axis to "Extinction", we have added the spectrum of nickel ferrite nanoparticle. We have added relevant explanations to the manuscript. The shoulder in the UV-Visible spectrum at lower wavelength region is typical for Au NPs.

4. Figure 2: The spelling of "Wavelength" is incorrect.

Reply: Thank you, we have corrected that.

5. Line 173-178: The authors said that smaller gold seeds (about 2-3 nm) are found to develop while reducing chloroauric acid on the surface of nickel ferrite nanoparticles as observed in ТЕМ. This seems real but no literature is cited. The following literature will support their observation; Khoury, Rami A., et al. "Monitoring the Seed-Mediated Growth of Gold Nanoparticles Using in Situ Second Harmonic Generation and Extinction Spectroscopy." The Journal of Physical Chemistry С 122.42 (2018): 24400-24406.

Reply: Thanks for Your suggestion; we have added the paper to ‘References’.

6. The authors said that they have used dynamic light scattering measurements to characterize their nanoparticle but could not see any data on the manuscript. The size measurement from DLS would be helpful to support their ТЕМ Also, please report the polydispersity index of nanoparticles.

Reply: It is a technical mistake. We had intention to determine particle size by DLS technique before the Covid-19 pandemic. Unfortunately, in Russia lockdown restrictions are not over yet. This study will be the aim of our future paper.

 

7. The manuscript lacks some important relevant literature which seems essential to support their claim behind the synthesis of core-shell nanoparticles. I would suggest adding the following papers;
8. Work from Naomi Halas group from Rice University such as "Carly S. Levin,
   Cristina Hofiman, Tamer A. Ali, Anna T. Kelly, Emilia Morosan, Peter Nordlander,
   Kenton H. Whitmire, and Naomi J. Halas. Magnetic-Plasmonic Core-Shell
   Nanoparticles. ACS Nano 2009, 3, 1379-1388."
9. Similarly, the paper from Louis Haber research group from Louisiana State
   University; "Kumal, Raju R., et al. "Near-infrared photothermal release of SiRNA
   from the surface of colloidal gold-silver-gold core-shell-shell nanoparticles studied
   with second-harmonic generation." The Journal of Physical Chemistry С 122.34
   (2018): 19699-19704."

Reply: Thanks for your suggestion; we have added the papers to ‘References’.

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Authors have answered most of the questions. 

Corrections have been made in the text.

The paper is thus suitable for publication.

Author Response

We are thankful to Reviewer for their careful reading of the manuscript, the criticism, and their constructive comments which allow us to improve the paper

Reviewer 4 Report

This paper is ascribed to the synthesis of magnetic NiFe2O4 nanoparticles (NPs) by well-known co-precipitation approach covering them later with thick gold shell by methionine induced reduction of gold acid species. The results presented can be interested for technologist involved in the synthesis of hybrid core-shelled particles. However, the authors should correct and explain some statements.

- In the title, Au@NiFe2O4 NPs are formed and studied whereas in the main text – NiFe2O4@Au. Please correct the title because the shell is gold.

- In the ‘Abstract’ part it is reported that the hybrid NPs synthesized in this study can be applied for magnetic resonance imaging, hyperthermia and so on. However, any experimental verifications of these statements are presented in the paper. Also, ‘magnetic hyperthermia’ and ‘cancer’ words should be rejected from the paper ‘Keywords’.

-  According to the ‘Materials and Methods’ part, the synthesis of Ni ferrite NPs was conducted during 5 min whereas in the ‘Results’ part this procedure lasted 2 h. Please correct.

- In the ‘Experimental’ part the way by which the size distribution histogram was determined should be presented since TEM image (Fig. 1c) demonstrated highly agglomerated particles.

- From the XRD patterns the peaks, indicating the size of gold-coated magnetic NPs obtained by single deposition step, differ insignificantly from ones coated by three steps but the content of deposited gold and the final size of NPs differ drastically. Please explain.

- In the ‘Conclusions’ part, it is stated that “We propose a method that uses amino acid methionine as a reducer of gold species and stabilizing agent for NPs. However, this method has been presented clearly in the manuscript published by other scientists in J. Phys. Chem. 2015, 119, 117398. Please correct statement.

- The caption for Figure 5 is required.

- Please change ‘u’ (line 227, p.7) to ‘and’.

Comments for author File: Comments.pdf

Author Response

We are thankful to Reviewer for their careful reading of the manuscript and their constructive comments which allow us to improve the paper

Round 3

Reviewer 4 Report

This manuscript after careful revision looks publishable without further corrections. I not against the acception of this work for publication.