Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers
Round 1
Reviewer 1 Report
Very similar review articles have been published (Coord. Chem. Rev. 2020, 405, 213139; Cells 2022, 11, 4029; Med. Res. Rev. 2023:1-22. Doi:10.1002/med.21964) and they have covered most of the research articles. Therefore, to my opinion this review is not suitable for this journal which has much higher impact.
Meanwhile, this article summarized the developments of multi-functional boron-delivery agents. They discussed both small molecule-based peptide, porphyrin and macromolecule-based boron agents (nanocarriers such as liposomes and nanoparticles). The writing is very concise, but the review is poorly organized.
Author Response
This is an invited manuscript for a Special Issue of Cancers entitled "Boron Neutrons Capture Therapy: Critical Issues and Future Prospects", with Editors R. Barth and N. Gupta. This invited review article was especially written to highlight the 5 most promising boron delivery agents for BNCT reported to date, not an exhaustive review of all known boron agents.
Reviewer 2 Report
This paper presents an "almost" comprehensive review on boron delivery agents. This review provides the reader with a general overview of a list of the 3rd generation boron delivery agent and with an emphasis on the multi-functional boronated molecules and boron nanoparticles as a promising delivery agents for BNCT. I strongly suggest the author to expand the list of boron nanoparticles to other boron-rich nanoparticles such as boron nitride, BCNO, and boron phosphate nanostructures which have been shown as a promising delivery agents for BNCT.
Author Response
We expanded the boron nanoparticle section, as suggested by the reviewer
Reviewer 3 Report
This paper summarized the development of the Multi-Functional Boron-Delivery Agents for BNCT in this decade. And point that tumor-targeted boron delivery agents that are radio-labeled or linked to a fluorophore, and able to deliver therapeutic amount of 10B to tumors with high T/N and T/B, are promising multi-functional agents for BNCT. I agree with the publication of this article. The following aspects are some suggestions to make the reader known better of this work:
1. Line 45, “BNCT has been used clinically for over 50 years for the treatment of difficult to treat cancers,” The first clinical studies of BNCT took place in the 1950s and early 1960s by Lee E. Farr, James S. Robertson and Elmer E. Stickley of Brookhaven National Laboratory and William H. Sweet, Gordon L. Brownell and Soloway of the Massachusetts General Hospital and the Massachusetts Institute of Technology. So BNCT clinical application has a history of over 60 years.
2. Line 52, “…. thermal (0.025 eV) or epithermal (10,000 eV) neutrons…” According to IAEA report TECDOC-1223, for the purposes of reporting beam intensity, the common definition for an epithermal energy range should be used, namely 0.5 eV to 10 keV. Thermal neutron energy range is ＜0.5eV.
3. Line223, “…showed to have low toxicity toward V97 lung and human glioma…” Please make sure it is V97 or V79 cell.
4. Some recent developments, like exosome-coated 10B carbon dots, multifunctional high boron content MOFs nano-co-crystals and covalent organic framework, are designed as multifunctional boron delivery agents for BNCT. These latest works might be suitable to be mentioned in this review.
Author Response
We made all the corrections suggested by the reviewer and expanded the boron nanoparticle section of the review article.
Reviewer 4 Report
The manuscript "Multi-functional boron-delivery agents for boron neutron capture therapy of cancers" reviews different classes of boron-delivery agents and their application to cancer therapy. To this end, agents based on peptides, antibodies, porphyrins, nanoparticles, and liposomes have been discussed. However, the overall subject is interesting; the current version has some flaws and lacks some details that need to be addressed carefully and thoroughly before the paper can be endorsed for publication. For example:
1. In the introduction, highlight earlier published reviews and the strength of this review.
2. I do not see the use of "simple summary" before the abstract; delete it.
3. Authors should dedicate a section highlighting the pros and cons of BCNT. Besides, its advantages over other modalities should also be discussed.
4. Specify the type of cancer for BSH, L-BPA, and 3-BPA.
5. A table(s) containing the data of compounds (e.g., 9-13; 18-20), brand name (if any) and their application would enhance the value of the manuscript.
6. Figure 6, compound 15: What are 88, 89 and 90?
7. Authors should check the manuscript and define/explain the abbreviations.
8. Include a section on future perspectives and suggestions before the conclusion.
Author Response
The "Simple Summary" was included in the template. It is up to the Editor if it needs to be removed. Several early review articles are included in the list of references. The pros and cons of BNCT are discussed in other contributions to this special issue on BNCT, our invited review has the goal to highlight the 5 most promising boron delivery agents reported to date. Likewise, other contributions to this special issue discuss the types of cancers that have been treated using BNCT, our review discusses mainly the boron delivery agents. Figure 6 was revised and abbreviations were defines, as suggested by the reviewer.
Round 2
Reviewer 1 Report
Very similar review articles have been published (Coord. Chem. Rev. 2020, 405, 213139; Cells 2022, 11, 4029; Med. Res. Rev. 2023:1-22. Doi:10.1002/med.21964) and they have covered most of the research articles. Therefore, to my opinion this review is not suitable for this journal which has much higher impact.
