This manuscript was reviewed carefully. This paper reported an entangled gel structure comprising an organic nanorod (cellulose nanocrystal (CNC)) and inorganic nanodisk (Laponite (LAP)) to perform a combination of starvation therapy (ST), chemodynamic therapy (CDT), and photothermal therapy (PTT) for localized cancers. The ICG/GOx/Cu-installed CNC/LAP gel used in combination with NIR laser realized improved anti-proliferation, cellular reactive oxygen species (ROS), cellular GSH degradation, and apoptosis in colorectal cancer (CT-26) cell. However, there are concerns with the experimental data and design of this study. The article introduces too many elements of investigation, such as ICG, Gox, Cu, etc., so that there is confusion when setting up the experiment and analyzing the results at the end. Overall, I think the manuscript is worthy considering for publication after an effective revision.
The author attempts to conduct anti-tumor treatment through the combined action of ST, CDT and PTT, but the author does not provide a detailed review to introduce the intrinsic connection between the three elements (GOx, Cu and ICG), the ingeniousness of the designed structure of nanogel, and the synergistic effect between the three anti-tumor stratrgies. If the author does not summarize the points I mentioned in the introduction and discuss the synergistic effect in the experimental design and results, simply encapsulating the three substances ABC to examine the three treatment methods respectively, the research presented in this way has no innovative significance. Introduction part, if possible, some important and relative reports about CNC mediated chemodynamic therapy can be cited to enrich the background of this paper. Please see references (Carbohydrate Polymers, 2022, 289, 119432; Carbohydrate Polymers, 2021, 258, 117685 ).
In addition, there are still some puzzling points in the manuscript that need to be carefully reviewed by the authors. For example, in the photothermal activity test, The results of Figure 5a show that the samples without ICG (CNC/LAP, CNC/GOX/Cu/LAP) have little thermal imaging performance in solution, why the samples of these two groups that were injected into the mice showed red areas of thermal imaging? it is incomprehensible. The author did not indicate the sample volume injected here. According to our previous experience, the volume of each injection will not exceed 200 μl. It is difficult for ICG to have such a strong thermal imaging effect after 14 days at such a low concentration.

The authors have addressed the comments and it can be accepted in current version. In addition, since the author designed a CNC-based gel network, a recent review (International Journal of Biological Macromolecules, 2022, 222, 1500-1510. DOI: 10.1016/j.ijbiomac.2022.09.266) of CNC applications in drug delivery can deeply highlight the unique use of CNC in this study, and it is best to cite it if possible.