Synthesis of poly(acrylic acid) coated magnetic nanospheres via a multiple polymerization route

Magnetic nanospheres are versatile candidates for both fundamental and practical applications. Before they are applied in more complicated fields, their surface must be modified by several functionalities. However, the surface modification can be affected by the magnetic nanoparticles (MNP) embedded in the polymer matrix. Herein, the synthesis of poly(acrylic acid) coated magnetic nanospheres via a multiple polymerization route is described. During the synthesis process, seed emulsion polymerization was applied to redistribute the MNP in the polymer matrix, and the relationship between the structure of magnetic nanospheres and the thickness of the grafted poly(acrylic acid) layer was investigated. The development of size, morphology and magnetic properties of the nanospheres were characterized by transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, X-ray diffraction and vibrating sample magnetometry. This work would pave the way to design and preparation of new structure of functional magnetic nanospheres with precise surface modification.


Comments to the Author(s)
The submitted manuscript proposed preparation of poly(acrylic acid) coated magnetic nanospheres (PMNS) via a multiple polymerization route. In general, this work is written clearly, but some experiment design and characterization results are inadequate and the claims author proposed here don't have sufficient evidence to support. Some comments attached as follows: 1、In the Introduction part, a problem was presented that magnetic nanoparticles would migrate to the surface of the nanospheres during the process of miniemulsion polymerization, and further affected the further surface modification by functional groups. Aimed to this topic, author proposed a multiple polymerization route to overcome it. However, in all subsequent experimental results described in this work, there was no direct evidence or convincing data to support the multi-step polymerization approach did not affect subsequent surface modification.
For example, what is the difference in the density of the surface functional groups or the thickness of the PAA layer on the surface of the magnetic microspheres obtained from the multistep polymerization method compared with the conventional emulsion polymer method? 2、In the 3.6 Characterization, did the TGA data be measured in nitrogen atmosphere ? It should be described clearly. 3、In the last sentence of 4.1.2, it should hydrodynamic size increased by 50 nm rather than size increased by 50 nm. 4、In the part of 4.1.3, the saturation magnetization of MNS1 and MNS2 should directly give the actual saturation magnetization measured by VSM firstly, without subtracting the mass of ligands and polymers on the surface of magnetic particles. Only with such data could make the readers understand intuitively the magnetic properties of the obtained magnetic microspheres in this work. 5、In the part of 4.2.1, MNS2 should be set as the control group when studying the particle size of microspheres varies with the increase of pH. That is to say, the particle size of MNS2 varies with the increase of pH must be measured.

15-Apr-2019
Dear Dr chen: Title: Synthesis of poly(acrylic acid) coated magnetic nanospheres via a multiple polymerization route Manuscript ID: RSOS-190141 Thank you for submitting the above manuscript to Royal Society Open Science. On behalf of the Editors and the Royal Society of Chemistry, I am pleased to inform you that your manuscript will be accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the reviewers' comments at the end of this email.
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Reviewer: 2
Comments to the Author(s) The submitted manuscript proposed preparation of poly(acrylic acid) coated magnetic nanospheres (PMNS) via a multiple polymerization route. In general, this work is written clearly, but some experiment design and characterization results are inadequate and the claims author proposed here don't have sufficient evidence to support. Some comments attached as follows: 1、In the Introduction part, a problem was presented that magnetic nanoparticles would migrate to the surface of the nanospheres during the process of miniemulsion polymerization, and further affected the further surface modification by functional groups. Aimed to this topic, author proposed a multiple polymerization route to overcome it. However, in all subsequent experimental results described in this work, there was no direct evidence or convincing data to support the multi-step polymerization approach did not affect subsequent surface modification.
For example, what is the difference in the density of the surface functional groups or the thickness of the PAA layer on the surface of the magnetic microspheres obtained from the multistep polymerization method compared with the conventional emulsion polymer method? 2、In the 3.6 Characterization, did the TGA data be measured in nitrogen atmosphere ? It should be described clearly. 3、In the last sentence of 4.1.2, it should hydrodynamic size increased by 50 nm rather than size increased by 50 nm. 4、In the part of 4.1.3, the saturation magnetization of MNS1 and MNS2 should directly give the actual saturation magnetization measured by VSM firstly, without subtracting the mass of ligands and polymers on the surface of magnetic particles. Only with such data could make the readers understand intuitively the magnetic properties of the obtained magnetic microspheres in this work. 5、In the part of 4.2.1, MNS2 should be set as the control group when studying the particle size of microspheres varies with the increase of pH. That is to say, the particle size of MNS2 varies with the increase of pH must be measured.

Dear Editor，
We have revised our manuscript according to the reviewers' comments and the revised texts have been highlighted by "Track Changes" in MS Word. We appreciate the detailed and useful comments and suggestions from you and the reviewers. The point-by-point answers to the comments were listed as below.

R1:
In this manuscript, Chen, et al, reported a multiple polymerization route to synthesize poly (acrylic acid) coated magnetic nanoshperes with controlled surface modification. The obtained magnetic nanospheres were fully characterized by XRD, TGA, TEM, DLS, and VSM. Besides, the relationship between the structure of magnetic nanospheres and the thickness of the grafted poly (acrylic acid) layer has been investigated. This work provided a new idea to control the structure and surface of magnetic polymer nanospheres. Therefore, I recommend that this work can be published in RSOS after addressing some specific issues as follows: Answer: We thank this reviewer's careful reading and good understanding of our manuscript.
Below we will list the corresponding revisions made in our revised manuscript to meet the reviewer's comment. Answer: We thank the reviewer for his/her valuable advice. In Figure 6, we added hydrodynamic sizes at extreme pH (pH 3 and pH 11). In line 9, section 4.2.1, the discussion for size at extreme pH is added as "PMNS is unstable at low pH (pH ≤ 4) because of insufficient space hindrance and reduced electrostatic repulsion." Answer: Actually, the amount of magnetic content can be adjusted. However, we take the magnetic content of 5wt% as an example to study the effect of multi-step polymerization on the functional modification of magnetic microspheres. In our future work, we will focus on the magnetic content effect on the preparation process.

How the stability of the poly (acrylic acid) coated magnetic nanoshperes in PBS?
Answer: Poly (acrylic acid) coated magnetic nanoshperes can be stored for up to 6 months in PBS solution without precipitation. We added "The MNS2 showed a large amount of precipitation in one month. While the PMNS stored in a PBS buffer was stable for up to 6 months without precipitation, which demonstrated that the poly(acrylic acid) chains endow PMNS a good stability." in line 10, section 4.2.1 in the revised manuscript. Figure 5, "loop" should be "loops" Answer: We thank the reviewer for pointing out the typo and it has been corrected.

Answer:
We thank the reviewers for their valuable suggestions for related references. We have carefully reviewed the literatures and cited them in the revised manuscript as ref [15] in line 12, section 2, and ref [17] in line 12, section 2, respectively.

R2:
The submitted manuscript proposed preparation of poly(acrylic acid) coated magnetic nanospheres (PMNS) via a multiple polymerization route. In general, this work is written clearly, but some experiment design and characterization results are inadequate and the claims author proposed here don't have sufficient evidence to support. Some comments attached as follows: Answer: We thank this reviewer's careful reading and good understanding of our manuscript.
Below we will list the corresponding revisions made in our revised manuscript to meet the reviewer's comment. Answer: We thank the reviewer for this question. Here, we are sorry for the reviewer's confusion on the motivation of our manuscript because of our improper presentation. In this work, poly(acrylic acid) coated magnetic nanospheres were prepared by a multipolymerization method, which is an alternative route for preparation of functional magnetic nanospheres with controlled structure. It is also proposed that the seed emulsion polymerization method can be used to control the aggregation morphology of MNP in magnetic microspheres and the distribution of MNP to affect the surface functionalization. To avoid the confusion, we revised some sentences in the introduction. In line 22, section 2, We have deleted the " However, MNP would migrate to the surface of the nanospheres in some cases, which affect the further surface modification by functional groups [37]. To avoid this negative effect, efforts have been made by researchers."Then，in line 24, section 2, add "In order to further improve the encapsulation of magnetic nanoparticles" later. In line 28, section 2, add "Therefore, we provide an alternative way to prepare functional magnetic nanospheres." In line 33, section 2, add " At the same time, the effect of aggregation state of magnetic nanoparticles in magnetic nanospheres on surface functionalization was also studied." In order to make the paper's data more convincing, we compare it with traditional aggregation methods. In line 15, section 4.2.2, add " Xu used a seed emulsion polymerization method to increase the thickness of functional layer by ~10 nm [19]. Compared with the literature, our method improves the layer thickness to some extent." 2. In the 3.6 Characterization, did the TGA data be measured in nitrogen atmosphere ? It should be described clearly.
Answer: TGA was carried out in air atmosphere instead of nitrogen atmosphere. In line 3, section 3.6, "The thermogravimetric analysis (TGA) model Q600 SD was used to analyze the magnetite content at a heating rate of 10 °C/min." was corrected to "The thermogravimetric analysis (TGA) model Q600 SD was used to analyze the magnetite content at a heating rate of 3. In the last sentence of 4.1.2, it should hydrodynamic size increased by 50 nm rather than size increased by 50 nm.
Answer: It has been corrected according to the reviewer's suggestion in the revised manuscript. Answer: We thank the reviewer for pointing out this question. We provided a more intuitive data description as shown in Figure 5a. Add " In Figure 5a, the saturation magnetizations of MNP, MNS1 and MNS2 are 52.4 emu/g, 2.7 emu/g and 0.96 emu/g, respectively. " in line 2, section 4.1.3.

5.
In the part of 4.2.1, MNS2 should be set as the control group when studying the particle size of microspheres varies with the increase of pH. That is to say, the particle size of MNS2 varies with the increase of pH must be measured.

Answer:
We did the control experiments and added the data to Figure 6b. In line 7, section 4.2.1, we added text as "With the increase of pH value, the hydrodynamic size of MNS2 is almost a constant, because MNS2 has no pH sensitivity."