A Novel Approach for Enhanced Osteosarcoma Photodynamic Therapy Using Encapsulated Methylene Blue in Silica Nanoparticles
, Abdulsalam Abuelsamen 3, Samer H. Zyoud 4, Mohammad A. Mhareb 5, Azlan Abdul Aziz 6 and Osama Abu Noqta 1
Round 1
Reviewer 1 Report
The authors report a drug delivery system of a photosensitizer loaded silica nanoparticles for photodynamic therapy. The following issues have to be addressed before it can be published.
1. For the fabrication of MB-SiNPs, details of the original concentrations of MB added in the solution to get various concentrations MB encapsulated with SiNPs should be given. The loading efficiency should be analyzed.
2. In figure 1, the absorption spectra of free MB and MB-SiNPs should be given.
3. In figure 5, the results show obvious dark toxicity of MB-SiNPs at 1.25 µM. What is the reason for this?
4. For the PDT of cell, the cells were suspended in media or grown on the cell plate? In the experimental part, it seems that the PDT process was conduced in cell suspensions. Generally, after incubation of NPs with cells, the NPs not uptaken by cells should be washed away before light exposure.
5. The uptake of NPs by cells should be characterized by fluorescence imaging.
Author Response
Dear Reviewer,
We would like to express our gratitude for your positive feedback and valuable comments regarding our manuscript. We appreciate your time and effort in carefully reviewing our work and providing insightful suggestions for improvement. We are pleased to note that all the reviewers recommend publication of our work once the suggested modifications have been made.
We have taken great care to address all the concerns raised by you and have made the necessary changes to the manuscript accordingly. We have provided detailed responses to all comments and incorporated the suggestions in a constructive and coherent manner. We are confident that the revised manuscript meets the standards of the Journal of Composites Science and is suitable for publication.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The paper is clearly written and relatively novell. Imisst there only one information about the influnce of silica nanoparticles in the body.
Author Response
Dear Reviewer,
We would like to express our gratitude for your positive feedback and valuable comments regarding our manuscript. We appreciate your time and effort in carefully reviewing our work and providing insightful suggestions for improvement. We are pleased to note that all the reviewers recommend publication of our work once the suggested modifications have been made.
We have taken great care to address all the concerns raised by you and have made the necessary changes to the manuscript accordingly. We have provided detailed responses to all comments and incorporated the suggestions in a constructive and coherent manner. We are confident that the revised manuscript meets the standards of the Journal of Composites Science and is suitable for publication.
Author Response File: Author Response.docx
Reviewer 3 Report
In this study, an extensive analysis of the size and shape evolution of the synthesized silica nanoparticles loaded with MB was conducted using TEM. Various encapsulated and bare MB concentrations were tested for cytotoxicity against osteosarcoma cells. Some minor issues should be addressed before publication:
(1) Page 2, Line 58, An unnecessary space appears after "[4].";
(2) Page 3, Line 118, the "2" in "CO2" should be subscript format (also in Page 3, Line 149);
(3) Page 5, Figure 3, the error bars should be standard;
(4) Page 6, Figure 4, There are some garbled codes in the Figure 4 (also in Page 7, Figure 5 and Figure 6);
(5) Page 8, Figure 7 is not very clear, the authors are suggested to redraw it;
Overall, the paper is well organised and can be accepted after minor reversion.
Author Response
Dear Reviewer,
We would like to express our gratitude for your positive feedback and valuable comments regarding our manuscript. We appreciate your time and effort in carefully reviewing our work and providing insightful suggestions for improvement. We are pleased to note that all the reviewers recommend publication of our work once the suggested modifications have been made.
We have taken great care to address all the concerns raised by you and have made the necessary changes to the manuscript accordingly. We have provided detailed responses to all comments and incorporated the suggestions in a constructive and coherent manner. We are confident that the revised manuscript meets the standards of the Journal of Composites Science and is suitable for publication.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
My new comments are highlighted in blue.
I do not think the authors have replied to my questions properly. I do not recommend its publication.
Reviewer 1 Comments:
The authors report a drug delivery system of a photosensitizer loaded silica nanoparticles for photodynamic therapy. The following issues have to be addressed before it can be published.
1) For the fabrication of MB-SiNPs, details of the original concentrations of MB added in the solution to get various concentrations MB encapsulated with SiNPs should be given. The loading efficiency should be analyzed.
Author’s response: The basic concentrations of methylene are not important to mention because during encapsulation, the samples are purified through a dialysis membrane. As a result, higher basic concentrations can be used. However, the most important aspect at this stage is to ensure the complete removal of any unencapsulated methylene molecules.
If the authors think the feeding concentrations of MB are not important, please clarify how did you get MB-SiNPs with five concentrations of MB? It is very important to know the feeding concentrations of MB and the loading efficiency should also be analyzed.
4) For the PDT of cell, the cells were suspended in media or grown on the cell plate? In the experimental part, it seems that the PDT process was conduced in cell suspensions. Generally, after incubation of NPs with cells, the NPs not uptaken by cells should be washed away before light exposure.
Author’s response: The cells were grown on the plate overnight, and then the NPs were added and incubated together overnight. Some of the NPs attached to the cell membrane. The suspended NPs had no effect on the cells when exposed to light. However, we washed them directly after PDT.
Do you have any evidence to support your claim that the suspended NPs do not have any effect on the cells? Actually, the suspended NPs in the media will also generate sufficient ROS to destroy cell membrane.
5) The uptake of NPs by cells should be characterized by fluorescence imaging.
Author’s response: Thank you for your valuable comment. We completely agree with you that fluorescence imaging is an important aspect to consider in the characterization. In response to your suggestion, we plan to conduct fluorescence imaging testing on the NPs. We will include these results in our future work as a separate manuscript to provide a more comprehensive evaluation of the particles. Thank you again for your insightful comment.
Fluorescence cell imaging is one of the most normal experiments for NPs delivery and cell PDT. At least you need to know whether your NPs can enter cells, then perform PDT.
Author Response
Dear reviewer,
Thank you for taking the time to review our manuscript and for providing your valuable feedback. We greatly appreciate your insightful comments and suggestions which have helped us to improve the quality of our work.
We are pleased to inform you that we have carefully considered all your comments and concerns, and have made the necessary revisions to the manuscript as per your suggestions. We have also provided detailed responses to all the questions and comments raised by you.
We are confident that you will find the revised version of the manuscript to be suitable for publication in the Journal of Composites Science after incorporating all the requested modifications. We sincerely hope that all the appropriate changes have been made and that the manuscript is now more precise and suitable for publication.
Once again, we would like to express our gratitude for your time and effort in reviewing our manuscript. We look forward to your positive feedback on the final revised version.
Sincerely,
Tariq AlZoubi (on behalf of all authors)
Associate professor of Physics
College of Engineering and Technology
American University of the Middle East
Author Response File: Author Response.docx
Reviewer 2 Report
The author adessed my comments and I recommend the text for publication.
Author Response
Thank you for your great effort and time in reviewing our work and accepting our manuscript for publication.
Reviewer 3 Report
The authors have addressed all my concerned and the paper can be accept in the present form.
Author Response
Thank you for your great effort and time in reviewing our work and accepting our manuscript for publication.
