The work conducted by Cassioli et al. is promising and well-organized and would be an addition to the scientific community. However, I have some major concerns that should be addressed before this work could be accepted for publication:
1. Please mention the in vitro release findings in the abstract.
2. What is the stability of the designed system at acidic pH (5.5 and 6.5). This should be added to give insights into the stability of this system at different sites inside the body.
3. A statistical analysis section should be added in the methodology part stating which software is used, at what values are the data significant, etc.
4. The whole study should be statistically interpreted, stating the number of independent experiments conducted, significant differences compared to positive controls, probability, etc.
5. The authors should discuss and detail the benefit of conducting the release study at physiological and acidic pH (cancerous). This is a good point to be considered to highlight the significance of the study.
6. More chemical confirmatory tests should be conducted to confirm the successful loading of the cargo, such as FTIR, TGA, etc.
7. Please create histograms from the TEM images and, calculate the average size from these histograms, and compare them to zeta size values. This is indicative of the actual size and not the hydrodynamic size.
8. The MTT assay findings should be compared to positive control.
9. More mechanistic anticancer assays, such as apoptosis (Flow cytometry), cell cycle analysis, cell migration, RTQPCR for overexpressed genes, etc., should be conducted to predict the anticancer mechanism.

The authors responded very well to all issues raised by reviewers. I recommend acceptance in the present form.