pH-sensitive thiamethoxam nanoparticles based on bimodal mesoporous silica for improving insecticidal efficiency

In this study, we synthesized pH-sensitive thiamethoxam-3-(2-aminoethylamino) propyl-bimodal mesoporous silica (P/Thi-NN-BMMs) nanoparticles (NPs). We used this bimodal mesoporous silica (BMMs) mesoporous material as a carrier based on the principle of free radical polymerization. The size of the P/Thi-NN-BMMs NPs was about 891.7 ± 4.9 nm, with a zeta potential of about −25.7 ± 2.5 mV. X-ray powder diffraction analysis, N2-sorption measurements and thermogravimetric analysis indicated that thiamethoxam (Thi) was loaded into the pores of the mesoporous structure and that the mesopore surface was coated with polyacrylic acid (PAA). The loading rate of P/Thi-NN-BMMs was about 25.2%. The controlled-release NPs had excellent anti-photolysis performance and storage stability. The NPs showed significant pH sensitivity, and the Thi release rate in pH 10.0 phosphate buffer was higher than those in pH 7.4 and pH 3.0 phosphate buffers. We described the sustained-release curves according to the Weibull model. The relative toxicity of P/Thi-NN-BMMs against peach aphid was 1.44 times that of commercial Thi. This provides a promising instrument for effective insect control and environment protection.


Do you have any ethical concerns with this paper? No
Have you any concerns about statistical analyses in this paper? No

Comments to the Author(s)
The article is quite short. Introduction is really short. It will be nice if authors explain: i) why they have selected this nanoparticles, ii) why they coated them, iii) why they use Thi as active ingredient, and iv) what is the problem and/or target. Further there are some important missing references: for example, during the introduction, experimental methods. Authors need to address this issue.
During the abstract, there are some abbreviations that need to be explained during the abstract (i.e. BMMs). They need to add particle size and z-potential average. In fact, why they are performing DLS in water? It is like a simulated insect gastrointestinal media?
During the introduction English must be improve. It is quite difficult to follow the discussion. There are some abbreviations that need to be explained during the introduction (i.e. THi) and it has to be extended.
No references about what a BBM is. Add some references as it is impossible to consider if they are good candidates for the release of pesticides or not, and to further compare with other porous silica materials. Add references here: "Double model mesoporous silica materials (BMMs) are a new type of mesoporous material with a worm-like pore of about 3 nm in a double-channel structure and a spherical particlestacking hole of about 10-30 nm (REF). BMMs are different from single-cell mesoporous materials and have many unique properties, such as controllable structure and controllable particle size (REF)." What are the main differences between "Double model mesoporous silica materials (BMMs)" and mesoporous silica? As I know mesoporous can be synthetized with a controllable structure and particle size.
I suppose that the release of Thi is performed at different pH as insect have to eat these particles and then the Thi will be released. But, what is a maximum particle size than a small insect can eat? Add this information in the introduction. Further add references here: "The pH of the digestive tract of herbivorous insects is mostly alkaline." In Figure 2, particles are really aggregated and it is quite difficult to distinguihsn the spherical morohlogy. Nanoparticles need to be dispersed and better SEM images (or TEM) need to be performed. DLS results show that particle size increases from 497 to 891 nm once Thi is loaded and the surface is covered with PAA. Is this increment due to the PAA or Thi in the surface? Comment on that. It the PAA size related with this difference on size (891 -497 = 394 nm). Do you have the characterization of the BBM+Thi or BBM+PAA combinations? Important characterization regarding the PAA-BMM coated nanoparticles (without Thi is needed) in order to assess the discussion. Authores need to add TGA, DXRP, DLS of PAA-BBM (without Thi) In the TGA indicate where are the 3 weight losses of Thi-NN-BMMS. Adde the TGA of Thi, as it will be easier to compare.
Add DRXP patterns. There is no figure related with this results.
How can the authors calculate the amount of encapsulated Thi? I cannot find this information along the text.

Decision letter (RSOS-200604.R0)
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Dear Dr Zhang:
Manuscript ID: RSOS-200604 Title: "pH-sensitive Thiamethoxam Nanoparticles Based on Double Model Mesoporous Silica for Improving Insecticidal Efficiency" Thank you for submitting the above manuscript to Royal Society Open Science. Your paper was sent to reviewers and their comments are included at the bottom of this letter.
In view of the concerns raised by the reviewers, the manuscript has been rejected in its current form. However, a new manuscript may be submitted which takes into consideration these comments.
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Your resubmitted manuscript should be submitted by 27-Oct-2020. If you are unable to submit by this date please contact the Editorial Office.
We look forward to receiving your resubmission.  5. The English of the manuscript should be improved and the mistakes of expression should be revised before publication. For example, "indicating that the influence, indicating that the amino functionalization, the loadingof thiamethoxam." "This indicated that encapsulation of the PAA polymer and Thi loading affected the order of the mesoporous structure and reduced the pore size."" These materials had better control against peach aphids." 6. In the experiment of RXRD, what did "d value" refer to? 7. What did LC50 refer to? The amount of thiamethoxam actually contained in the carrier or the total amount of the sample.
8. How to calculate the pesticide loading content of the P/Thi-NN-BMMs nano-pesticide while NN-BMMs still had weigh loss in TG curves? Why not use HPLC as performed in the test for the storage stability of P/Thi-NN-BMMs Nps.

Reviewer: 2
Comments to the Author(s) The article is quite short. Introduction is really short. It will be nice if authors explain: i) why they have selected this nanoparticles, ii) why they coated them, iii) why they use Thi as active ingredient, and iv) what is the problem and/or target. Further there are some important missing references: for example, during the introduction, experimental methods. Authors need to address this issue.
During the abstract, there are some abbreviations that need to be explained during the abstract (i.e. BMMs). They need to add particle size and z-potential average. In fact, why they are performing DLS in water? It is like a simulated insect gastrointestinal media?
During the introduction English must be improve. It is quite difficult to follow the discussion. There are some abbreviations that need to be explained during the introduction (i.e. THi) and it has to be extended.
No references about what a BBM is. Add some references as it is impossible to consider if they are good candidates for the release of pesticides or not, and to further compare with other porous silica materials. Add references here: "Double model mesoporous silica materials (BMMs) are a new type of mesoporous material with a worm-like pore of about 3 nm in a double-channel structure and a spherical particle-stacking hole of about 10-30 nm (REF). BMMs are different from single-cell mesoporous materials and have many unique properties, such as controllable structure and controllable particle size (REF)." What are the main differences between "Double model mesoporous silica materials (BMMs)" and mesoporous silica? As I know mesoporous can be synthetized with a controllable structure and particle size.
I suppose that the release of Thi is performed at different pH as insect have to eat these particles and then the Thi will be released. But, what is a maximum particle size than a small insect can eat? Add this information in the introduction. Further add references here: "The pH of the digestive tract of herbivorous insects is mostly alkaline." In Figure 2, particles are really aggregated and it is quite difficult to distinguihsn the spherical morohlogy. Nanoparticles need to be dispersed and better SEM images (or TEM) need to be performed. DLS results show that particle size increases from 497 to 891 nm once Thi is loaded and the surface is covered with PAA. Is this increment due to the PAA or Thi in the surface? Comment on that. It the PAA size related with this difference on size (891 -497 = 394 nm). Do you have the characterization of the BBM+Thi or BBM+PAA combinations? Important characterization regarding the PAA-BMM coated nanoparticles (without Thi is needed) in order to assess the discussion. Authores need to add TGA, DXRP, DLS of PAA-BBM (without Thi) In the TGA indicate where are the 3 weight losses of Thi-NN-BMMS. Adde the TGA of Thi, as it will be easier to compare.

Recommendation?
Accept as is

Comments to the Author(s)
The manuscript has met the standard for publication.

Review form: Reviewer 2
Is the manuscript scientifically sound in its present form? Yes

Do you have any ethical concerns with this paper? No
Have you any concerns about statistical analyses in this paper? No

Recommendation?
Accept as is

Comments to the Author(s)
Authors addressed all the mentioned issues.

Decision letter (RSOS-201967.R0)
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Dear Dr Zhang:
Title: pH-Sensitive Thiamethoxam Nanoparticles Based on Bimodal Mesoporous Silica for Improving Insecticidal Efficiency Manuscript ID: RSOS-201967 It is a pleasure to accept your manuscript in its current form for publication in Royal Society Open Science. The chemistry content of Royal Society Open Science is published in collaboration with the Royal Society of Chemistry.
The comments of the reviewer(s) who reviewed your manuscript are included at the end of this email.
Thank you for your fine contribution.  : RSOS-200604). We appreciate the prompt review of our paper and your encouraging decision. We appreciate the reviewers' comments and those comments are all valuable and very helpful for revising and improving our paper. We have revised the paper in accordance with the reviewers' suggestions. These changes will not influence the content and framework of the paper. We are looking forward to hearing from you regarding our resubmission. We would be glad to respond to any further questions and comments that you may have. Once again, thank you very much for your comments and suggestions.
The main corrections in the paper and the point-by-point responses to the reviewer's comments are as flowing.
Yours sincerely, Dr. Fang Zhang Beijing University of Technology E-mail: zhangfang2000@bjut.edu.cn Appendix A

REVIEWERS' COMMENTS AND AUTHOR' RESPONSES
Note: Our responses (standard typeface) to reviewers' comments (bold); the yellow highlighted words and sentences have been added to the main text. Response: We really appreciate the thoughtful suggestions made by the reviewer. We supplied some reports about polymer-coated nanomaterials and mesoporous silica applied in sustained release carrier in the introduction part, and added references [9][10][11][12][13] in the revised manuscript.

If possible, the sustained release curve should be fitted with different kinetics model to illustrate the mechanism of their sustained release performance.
Response: Thanks for the reviewer's comment. We added the release curve with different kinetics model to illustrate the mechanism of their sustained release performance, and the data was also provided in the revised manuscript (Table 2). Zero-order Where y was the fractional release of pesticide; x was the elapsed time; a0 was the kinetic release constant and a1 was constant. R 2 was the high value of linear regression coefficient.

Why do you choose pH 7.4 instead of neutral environment when studying the effect of pH value on the sustained release performance of the samples.
Response: The range of neutral phosphate buffer is usually between 5.5 and 8.5. It has been reported in some literature that phosphate buffer (pH 7.4) was often used as the neutral release medium when studying the effect of pH value on the sustained release performance of nano-pesticides [1][2][3] . We chose pH 7.4 instead of neutral environment according to the references . .

The BET surface and pore data results of Nitrogen adsorption-desorption isotherms should be listed.
Response: We greatly appreciate the thoughtful suggestions. According to the reviewer's suggestion, we conducted Nitrogen adsorption-desorption experiments, and the BET surface and pore volume of Nitrogen adsorption-desorption isotherms wereprovided in the revised manuscript. (Fig 4C, 4D) 5. The English of the manuscript should be improved and the mistakes of expression should be revised before publication. For example, "indicating that the influence, indicating that the amino functionalization, the loading of thiamethoxam." "This indicated that encapsulation of the PAA polymer and Thi loading affected the order of the mesoporous structure and reduced the pore size."" These materials had better control against peach aphids." Response: We are very grateful for the reviewers' comments. We have carefully revised the manuscript according to your kind suggestions, and the manuscript was polished by native English speakers. .

In the experiment of RXRD, what did "d value" refer to?
Response: The "d value" referred to the interplanar spacing, and the "d value" wasobtained by analyzing the spectrum. The X-ray diffraction phenomenon was based on the Bragg formula: 2d sin θ = nλ where "d" was the interplanar spacing in a certain direction of the crystal lattice, and θ was the glancing angle in the diffraction experiment. n was an integer and called the interference series.
7. What did LC50 refer to? The amount of thiamethoxam actually contained in the carrier or the total amount of the sample.
Response: Lethal Concentration 50(LC50) referred to the concentration of pesticide that caused 50% of the death of living organism. We added the information in the revised manuscript.

How to calculate the pesticide loading content of the P/Thi-NN-BMMs nano-pesticide while NN-BMMs still had weigh loss in TG curves? Why not use HPLC as performed in the test for the storage stability of P/Thi-NN-BMMs Nps.
2. During the abstract, there are some abbreviations that need to be explained during the abstract (i.e. BMMs). They need to add particle size and z-potential average. In fact, why they are performing DLS in water? It is like a simulated insect gastrointestinal media?
Response: Thank you very much. We added some abbreviations in the abstract of the revised manuscript. We determined the particle size and z-potential average, and supplied the data in the table 1 in the revised manuscript. The nanoparticles had good water solubility, and DLS was detected usually in water according to the previous reports [1,2] . What are the main differences between "Double model mesoporous silica materials (BMMs)" and mesoporous silica? As I know mesoporous can be synthetized with a controllable structure and particle size.
Response: We are very grateful for the reviewers' comments. According to the reviewer's kind suggestions, we explained the abbreviations in the introduction of the revised manuscript. The manuscript was polished by native English speakers. BMMs materials consisted of well-defined small mesopores of 3 nm as well as large interparticles pores. Whereas, the surface area typically lied in the 100-9 m 2 /g range, and the pore volume varies from 0.25-1.8 cm 3 /g. Therefore, compared with the traditional mesoporous material, the novel bimodal pore systems of BMMs material allowed the larger drug molecules easier accessibility to the active site due to disappearance of diffused limitation, and thereby improved the desired drug loading and release efficiencies and minimized the blocking influence of mesoporous channels. All these features of BMMs could provide an ideal medium for drug storage and controlled release [1,2] . 4. I suppose that the release of Thi is performed at different pH as insect have to eat these particles and then the Thi will be released. But, what is a maximum particle size than a small insect can eat? Add this information in the introduction. Further add references here: "The pH of the digestive tract of herbivorous insects is mostly alkaline." Response: Most of the pesticides used are currently dispersants and suspending agents with particle size of micron [1,2] . Compared with conventional pesticides, nano-pesticide has a greater dispersity due to its smaller particle size and better permeability into the epidermis of pests. It has been reported in some literature that the digestive system of insects is alkaline [3,4], and the pH value was higher than 7 in the sustained-release medium [5,6] . According to the reviewer's kind suggestions, we added the information and references in the introduction in the revised manuscript.