The manuscript entitled “Towards a deeper understanding of the synthesis of hollow periodic mesoporous organosilica (HPMO) nanospheres” describes the synthesis of a phenylene-based hollow mesoporous organosilica and evaluates their possible potential for medical applications. The manuscript can be divided into three main parts. In the first part, a selective silica etching strategy has been used for the synthesis of hollow mesoporous organosilica nanoparticles with a diameter of 480 nm. In the second part, the authors studied the effect of the size of the initial silica hard template, the time of etching, the dosage of etchant, and the manner of etchant addition on morphology and shell-thickness of final sphere materials. In the third part, the synthesized materials were loaded with rhodamine B and Zn-phthalocyanine dyes and then incubated with cancer cells to prospect for their use in biological and health applications. As a referee who is relatively familiar with mesoporous materials, I could just evaluate the work from the first two parts. To the best of my knowledge, the synthesis of HPMO with small-bridged organosilica by hard or soft template has been well documented. Therefore, there is not enough novelty for the first part of the manuscript which is ironically the main part of the work. Overall, the work in the current version does not have enough novelty for publication in the New Journal of Chemistry since the authors already conducted similar studies in J. Sol-Gel Sci. Technol. 2023, 107, 302-311. The manuscript may be suitable for another specific journal after addressing the following concerns:
1) It is well-documented that during the etching of a silica hard template under basic conditions, the redeposition of silica on the PMO shell is inescapable, as the authors also mentioned. Therefore, although a pure bridged organosilica was used in step 2, after the final step, a hollow mesoporous organosilica nanoparticle (HMON) was synthesized and not an HPMO nanoparticle, a finding was also confirmed by solid-state NMR as both T and Q bands are being observed. It is worth noting that the ratio of Q bands is higher than T bands. Therefore, I suggest that the authors highlight this aspect in the manuscript and change HPMO to HMON in the Title as well as the whole of the manuscript.
2) Authors have used FTIR spectroscopy to monitor selective silica etching. I think that the FTIR is not a careful technique since both the silica hard template and the PMO shell have similar peaks of Si-O-Si in their FTIR spectra. More importantly, the synthesis of HPMO or HMON by silica hard template is a well-known procedure and it is not actually needed to use FTIR investigation for its processes which is the main part of this manuscript.
3) The second study is interesting and if authors improve the related discussion of this part with an emphasis on the role of each reaction conditions on the thickness of final materials and its effect on the load capacity of rhodamine B and Zn-phthalocyanine, the quality of the manuscript may be improved
4) The dual-templating synthesis strategy should not be used for this work. Typically, this strategy refers to the synthesis of hollow materials by soft template synthesis when two different types of surfactants are used. It is recommended that authors do not use these terms since the synthesis of hollow mesoporous materials by hard template inherently is a dual-templating approach.
5) References should be updated. There is no relevant works reported after 2023.
6) Experimental Section including materials, characterization, synthesis etc. must be added to the manuscript or SI.
7) Page 5, Line7, “Bis-trimethoxysilyl ethane” must be changed to “1,4-bis-triethoxysilyl benzene”.
8) Page 6, Line 3, “pores etching” should be changed to “surfactant extraction”.
9) Page 6, , Lines 32, 36 and 41, what is the meaning of “?”?
10) Page 7, Line 45, “Figure S2” must be changed to “Figure S3”.
11) Page 7, Line 56, how did authors estimate the volume ratio of the hollow region? It is recommended that the related calculation and equation were added to Supplementary Information.
12) Page 8, Line 10, it seems that CTAB was not used for the synthesizing “amorphous BTEB”. The sample denoted as “amorphous BTEB” would not certainly be a mesoporous nanoparticle as the authors mentioned. It would be nonporous nanoparticles with a high loading of functional groups. Also, amorphous BTEB is confusing, I recommend to authors that phenylene-bridged silsesquioxanes (Ph-BSQ) nanoparticles be used.