Fructose-Based Metal–Organic Framework as a Means to Synthesize Sr-Loaded Chitosan Nanospheres with NLO Properties for Theranostic Applications in Radiotherapy
, Carlo Canepa 1, Leonardo Mortati 3, Antonio Alvarez de la Paz 4, Itzel Marisol Garnica-Palafox 4, Francisco Manuel Sánchez-Arévalo 4, Roberto C. Dante 5 and Domenica Marabello 1,2,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsIn this article, the authors prepare chitosan nanoparticles and ensure the loading with Sr ions by contacting the nanospheres with a Sr-fructose-based MOF. The manuscript is well written, and the results are adequately discussed. However, there are some remaining questions. After loading, how are the nanospheres separated from the MOF? How do you ensure that there is no Sr-fructose-based MOF loaded on the chitosan nanoparticles?
Other minor issues:
-There are repeated references: for example, references 14 and 28 are the same.
-Line 213: replace “ions” with “elements.”
Author Response
Comment 1: After loading, how are the nanospheres separated from the MOF?
Response 1: The Sr loaded nanospheres were separated from the unreacted MOF during the washing with water (section 2.1, lines 108-111), since the SrFRUCl MOF does not survive in water. A sentence was added at line 110 to clarify the issue.
Comment 2: How do you ensure that there is no Sr-fructose-based MOF loaded on the chitosan nanoparticles?
Response 2: The MOFs are “special” materials, that were formed only in solid state and in particular in crystalline form. Thus, the absence of peaks typical of the SrFRUCl MOF in the XRPD patterns (Figure 3) demonstrate that the MOF was not loaded on the chitosan nanoparticles. The FTIR spectra agree with the X-ray diffraction results. The discussion of the XRPD patterns was rewritten to clarify this issue (lines 202-204). I thank the referee to point out the mistake in figure 3, since the indication of the patterns of the Chitosan NPs+MOF and the Sr-NPs were exchanged. This glitches were corrected.
Comment 3: There are repeated references: for example, references 14 and 28 are the same.
Response 3: Thanks to the referee to point out these mistakes in the references: the double references were erased and consequently the references numbers were shifted.
Comment 4: Line 213: replace “ions” with “elements.”
Response 4: Done, thanks to the referee to point out this mistake.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe article titled "Fructose-based Metal Organic Framework as a means to synthesize chitosan nanospheres loaded with Sr with NLO properties for theranostic applications in radiotherapy" presents a novel 89Sr isotope carrier for radio-cancer therapy. Authors selected appropiate experiments for the characterization of the proposed material. They made an exhaustive work elucidating the critical role of fructose in the SrFRUCl MOF, being the key to loading Sr instead Cl ions.
The number of references is correct and the introduction brings the necessary context for the importance of this research. The methods used are described in detail and provide readers the instructions to reproduce the experiments, and the figures are in an excellent quality. I miss some extra experiments to resolve the lack of knowledge about the interaction between Sr and chitosan, but I understand that the data support the hipothesis of authors and maybe that study could be enough for another publication.
I suggest accept after minor correction of the following:
- Include the acronyms of Second Harmonic Generation, Active Pharmaceutical Ingredient and Metal Organic Framework immediately after definitions in abstract.
- I miss a scheme of the synthesis and proposed structure of the nanomaterial, to facilitate the understanding of the research to readers
Author Response
Comment 1: Include the acronyms of Second Harmonic Generation, Active Pharmaceutical Ingredient and Metal Organic Framework immediately after definitions in abstract.
Response 1: Done. Thanks to the referee to point out this omission.
Comment 2: I miss a scheme of the synthesis and proposed structure of the nanomaterial, to facilitate the understanding of the research to readers.
Response 2: The requested scheme was introduced in section 2.1. The reference to the article in which it was proposed the molecular structure of the CS/PVA hydrogel crosslinked by GA was also inserted.
Reviewer 3 Report
Comments and Suggestions for AuthorsIn this work, the author proposed the preparation of chitosan NPs using fructose-based MOF for the loading of 89Sr radionuclide for radiopharmaceutical treatments in cancer therapy.
The as-prepared products were roughly characterized by XRPD, FTIR,SEM and EDS. In my view, the presented results failed to lend support to the successful synthesis of desired products. Moreover, the author did nothing on the application of the synethesized products. Therefore, I can not recommend the publication of this work.
Comments on the Quality of English LanguageThe language should be improved by a native speaker.
Author Response
Comment 1: The as-prepared products were roughly characterized by XRPD, FTIR,SEM and EDS. In my view, the presented results failed to lend support to the successful synthesis of desired products.
Response 1: The Sr-loaded NPs were characterized with the most used techniques for polymer characterization, and also with the X-ray powder diffraction, since a crystalline material was involved in the synthesis. The referee should be more specific, and clearly indicate what further technique should be useful to better characterize the Sr-NPs.
Comment 2: Moreover, the author did nothing on the application of the synethesized products.
Response 2: The application of the synthesized product was stated in the title of the manuscript and discussed in the introduction.
Round 2
Reviewer 3 Report
Comments and Suggestions for AuthorsI have only minor remarks resp. recommendations: 1. This title of the work does not describe what the author did, 'Fructose-based Metal Organic Framework as a means to synthe- 2 size chitosan nanospheres loaded with Sr with NLO properties for theranostic applications in radiotherapy', because NLO properties and theranostic applications were not provided in the manuscript. 2. Actually, the current version of the manuscript was not greatly improved compared with the original one. 3. Please do more characterization and applications on the materials, for example, I would like to see TEM image and N2 adsorption-desorption isotherms to determine the pore size of the obtained products.
Comments on the Quality of English Language
The English is acceptable，but can be further improved.
Author Response
Comment 1: This title of the work does not describe what the author did, 'Fructose-based Metal Organic Framework as a means to synthe- 2 size chitosan nanospheres loaded with Sr with NLO properties for theranostic applications in radiotherapy', because NLO properties and theranostic applications were not provided in the manuscript.
Response 1: The NLO properties of the synthetized nanospheres are demonstrated in figure 13, since the Second Harmonic Generation is Non Linear Optical property of the second order. “Theranostic applications” means simply that the Sr loaded NPs can be used contemporary for “therapeutic applications”, if enriched with Sr-89 isotope, and for “diagnostic applications”, exploiting their SHG properties. This is discussed in the introduction and in the conclusions, since the work is a proof of concept, and its aim is to synthetize chitosan-based NPs with SHG properties loaded with Sr, that can be used for theranostic application.
Comment 2: Actually, the current version of the manuscript was not greatly improved compared with the original one.
Response 2: The original manuscript was modified according to the minor revisions requested by the referees.
Comment 3: Please do more characterization and applications on the materials, for example, I would like to see TEM image and N2 adsorption-desorption isotherms to determine the pore size of the obtained products.
Response 3: The chitosan nanospheres do not contain pores. The mechanism of capture of the Sr and Cl ions is not an adsorption-desorption process, since the ions were probably encapsulated on the chitosan matrix through coordinative, ionic, and hydrogen bonds. This was discussed in the section 2.3, were the results of ab initio calculations and Born-Oppenheimer molecular dynamics were reported.
