Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy

Round 1

Reviewer 1 Report

I suggest that the authors if possible can provide several graphs comparing the reviewed results. 

Author Response

Most of the results described in this review concern IC50 values. The latter can scarcely be compared between different works as the operating conditions and the type of cells used often change. For this reason we have reported only the values or ranges of values without carrying out a systematic comparison.

Reviewer 2 Report

The authors had a valuable study on bioconjugated transition metal complexes for cancer therapy. It is an important study in its field. In conjunction with those obtained in the last decades, have highlighted that the introduction of biologically relevant moieties in the coordination sphere
of transition metal centres can improve the selectivity and biocompatibility of metallodrugs. 

The work is a significant contribution to the field. It was well organized and comprehensively described. There are appropriate and adequate references to related and previous work. English used is correct and readable.

I have just some minor comments:

The abstract should be include the aim, background, method, results and conclusion.

The introduction is so long.

Points should be inserted after reference numbers.

Conclusion can improve. It dose not support the results.

Author Response

1) The abstract is very limited in terms of words (see guidelines), and therefore we thought we'd provide a very general overview of what will be presented in the review.

2) We believe that the presence of some fundamental general explanations on metallodrugs and their classifications are essential for the reader (especially the non-experts ones) to understand the contents presented in the review.

3) The mutual position of points and references is now correct.

4) We believe that the conclusions in this context must be quite general given the heterogeneity of the results presented. However, with the aim of further improving the manuscript, we have added some additional sentences in the conclusion section.

Reviewer 3 Report

The current manuscript discussed biologically relevant properties of biomolecule complexes with transition metals within anticancer therapy. The authors described the synthesis strategy of protein, peptide, nucleic acid, carbohydrate, and etc. metal-based conjugates, and consider the structure-activity relation, which marks their selectivity toward cancer cells and determines a highly important application of these compounds in the fight against cancer. 

This paper has the characteristics of a conventional review paper and shows a diligent accumulation of knowledge and its synthesis into a coherent narrative. In my opinion, the manuscript is suitable for a "systematic review". Accordingly, it must be structured according to the PRISMA requirements and guidelines, which can be found in the section "Instruction for the authors" on the MDPI official page. 

Author Response

Based on the invitation that we received from Applied sciences we believe that this contribution can be published as classical literature review.

Reviewer 4 Report

The review article submitted by Scattolin and coworkers is a detailed review of bioconjugated transition metal complexes employed in cancer therapy. The authors have drafted a comprehensive report covering different categories of metal complexes conjugated with various biomolecules implicated in cancer treatment. I do not have any particular comments about the content. I have a few minor concerns.

1.     Most of the figures are not properly referenced in the text. There is a number mismatched. Besides, figure 7 is incorrectly labeled as Figure 8.

2.     Lines 299-301 ‘A panel of cationic half-sandwich Ru(II) ……’ Please add a reference.

3.     Line 394 Authors mention the Bombesin peptide that has an N-terminal Cys. However, in Figure 8b (which should have been fig 7b) the Bombesin peptide does not have a Cys. Please make the necessary changes.

4.     Figure 10b on Mn CORMs cobalamine complexes: What does the pink box indicate? How are the ligands chemically attached to the cobalamine for compounds 69 to 72?

Author Response

1) The number and position of figures is correct.

2) we have added the missing reference (ref. 70)

3) the Cys residue is included in the M moiety reported in the figure. This formalism was used in the original paper. We have now uploaded a new version of Figure 8.

4) the alkynyl moiety is directly bounded to the cobalt of Vitamine B12 (cobalamine). We have modified Figure 15.