Nanotheranostics: Platforms, Current Applications, and Mechanisms of Targeting in Breast and Prostate Cancers
, Ikechukwu E. Peter 2,3,*, Akachukwu M. Onwuka 2,3, Bonaventure C. Obi 2,3,4, Maureen O. Akunne 2,5, Chukwuemeka S. Nworu 3, Paul M. Ejikeme 2,6,7, Theophine C. Akunne 2,3, Anthony A. Attama 1,2,* and Peter A. Akah 2,3Round 1
Reviewer 1 Report (New Reviewer)
The manuscript “Nanotheranostics: Platforms, Current Applications, Mechanisms of Targeting in Breast and Prostate Cancers” is certainly interesting, bringing advances of nanomedicine for theranostic application of cancer. However, the main problem is that breast and prostate cancers, which should be the focus of the paper, according to the title, are very little addressed throughout the manuscript. Particularly, there is no sufficient discussion of mechanisms of targeting in breast and prostate cancers, as the title implies. Furthermore, the figures seem to simple and do not add much compared to what is available in other papers.
“Any material employed in the formulation of a medicine that results in a finished product lesser than 1 micron in size is referred to as a nanoparticle”. Revise the definition. Most guidelines consider the 1-100 nm range. See FDA definition.
The introduction is too general. Add information of what is reviewed, in more details. There are numerous reviews already published on the field. Why is the present paper novel? State it clearly.
Figure 1 is too simple it adds nothing to the review. Improve it with many more details.
Include a column describing the main findings in table 1.
Solid lipid nanoparticles should come just after liposomes, due to similar lipid composition. Also, no application example for theranostics was given for solid lipid nanoparticle.
Better organize the nanosystems: group all lipid, polymeric and inorganic materials. For example, quantum dots are separate from other inorganic nanoparticles.
Overall, no discussion was supplied for the applications of different nanosystems for prostate and breast cancers, which should be the focus of the work (section 2). I understand that there is and application section (4), but not focusing on specific nanosystems.
Section 3 with just one paragraph is not useful.
Table 2: add the drug of each nanoparticle.
Table 3 should focus on nanomedicines used for prostate and breast cancers.
Section 6: include a section of monoclonal antibodies.
Trasferrin: what is the levels of the receptor expression on prostate and breast tumors? Same comment for other receptors addressed in the review.
Limitations: include a discussion of the limitations of the EPR effect and the need of tailoring nanoparticles for specific groups of patients for successful clinical trials.
No future perspective was given for prostate and breast cancers, which should the the focus. Same for the conclusion.
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report (New Reviewer)
Points of correction
1. Figures are not clear.
2. 2nd table needs an update. Add some more recent examples. “NCT 04951245” is correct?
3. Table 3 needs an update. The recent approval should be added.
4. Figure 3 is also incomplete and needs full information.
5. Figure 2 is incomplete and needs full details.
6. The abstract required rewriting to eliminate unnecessary words.
7. In the statement “The American Cancer Society rated the number of new cancer cases and death 37 in the United States to be approximately 1.9 million and 608,000 in 2021.” What about the recent statistic for 2022 and the number of cases of breast and prostate cancer?
8. The statement “The word “theranostics” refers to the 77 concurrently convergence of diagnosis and therapy.” Needs reference.
9. Check all abbreviations and write their full form in first use, like HPLC, EPR.
10. In part, “3. ADVANTAGES OF NANOTHERANOSTICS IN MEDICINE AND PHARMACY”. Provide significance with examples of breast and prostate cancer.
11. Make sure that each section explains your proposed title of the manuscript.
Moderate editing of English language required
Author Response
Please see the attachment
Author Response File: Author Response.pdf
Reviewer 3 Report (New Reviewer)
In this manuscript, Paul A. Akpa et al. summarized the common construction methods of nano-loaded drug platforms. The application of nano diagnosis and treatment platforms in medicine is reviewed, including visualizing drug release, visualizing biodistribution in real-time, non-invasively assessing target site accumulation, monitoring drug distribution at the target site, facilitating triggered drug release, predicting drug responses and evaluating drug efficacy longitudinally. At the same time, the targeting mechanism and related targeting ligands of nanomedicine platforms in vivo are summarized. The advantages of nano-diagnosis and treatment platforms in medical and pharmaceutical research, as well as the challenges and limitations of nano-therapeutics, are pointed out. I would like to recommend acceptance of this work after the following issues are addressed:
1. Page 2 lines 53-54, Revise the first sentence.
2. Page 2 line 59, ‘unresponsive treatment’ can be modified to ‘ineffective treatment’.
3. Page 3 line 90, The comma between ‘non-toxic’ and ‘and’ should be deleted.
4. Page 3, in the chapter about liposomes, the logic of the examples is not clear, and the characteristics of the relevant examples should be summarized and carried on in one sentence.
5. Page 4 line 126, Please delete 'Polysaccharides are used to make polymeric nanocarriers of organic sources', because it is not conclusive and representative.
6. Page 4 lines 126-166, This section provides an overview of the role of polymers in the construction of drug delivery platforms, so the material construction section should be highlighted in the description of the relevant examples.
7. Page 4-5 lines 167-190, Some examples of the application of metal and magnetic nanoparticles in cancer therapy should be listed, and their advantages and disadvantages should be evaluated.
8. Page 5, The application of carbon nanotubes in cancer therapy should be illustrated with some examples.
9. Page 8, Chapter ’ADVANTAGES OF NANOTHERANOSTICS IN MEDICINE AND PHARMACY RESEARCH’ should be merged into Chapter ‘APPLICATIONS OF NANOTHERANOSTICS’, and should not be treated as a separate part.
10. Page 12 lines 478-479, Does screening of targeted drugs through 'nanotheranostics' supported by relevant references, if so, add it.
11. The chapter’TARGETING MOIETIES/LIGANDS’ should be merged into the Chapter ‘MECHANISMS OF TARGETING OF NANOPARTICLES’.
12. Chapter ‘MECHANISMS OF TARGETING OF NANOPARTICLES’ should be placed after Chapter ‘NANOTHERANOSTIC PLATFORMS’
13. In the introduction of this review, the hazards of breast cancer and prostate cancer are discussed at great length, but the relevant applications are not focused on in the ‘APPLICATIONS OF NANOTHERANOSTICS’ section. Whether there are obvious advantages of nanomedicine in the treatment of breast cancer and prostate cancer should also be pointed out, please add relevant content.
Minor editing of English language required
Author Response
Please see the attachment
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report (New Reviewer)
Revision seems fine to me. The corrections made by the Author are satisfactory.
Minor editing of English language required.
Reviewer 3 Report (New Reviewer)
The authors answered my concerns and made revisions to the manuscript.
Good
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
1.Please add toxicological prespective of nanotheranostics..
2.what is the suggestion of this study for future works?
3.Please discuss and compare your results with previous works and add suggestions including Nanoantioxidanst based methods.
4.It will be better to add the role of mitochondria targeting using nanotheranostics.
5.Please add details for time period and dose selection from literatures.
6.More references for the discussion part of manuscript and update and bold your study novelty should be added: e.g.,
-DOI: 10.1016/j.trac.2019.05.004
-DOI: 10.1016/j.chemosphere.2022.134826
