The manuscript by Hosny et al designed and optimized the Rosuvastatin-Ellagic acid Nanotransfersomal ISG formulation to enable extended drug release for localized cancer therapy. To this end, they optimized formulation, particle size, entrapment efficiency and stability, and showed that RO-EA NTS-loaded ISG are stable, exhibit sustained release and that RO and EA exhibit a synergistic effect in inhibiting the growth of cancer cells. The content of the text clearly justifies the abstract. The authors should consider addressing the following concerns: 1. The title may be misleading and needs to be corrected. It may imply that the ISG loaded drug NTS have the intrinsic ability to inhibit proliferation. However, it is only the drugs (or the combination thereof) have enhanced anti-proliferative activity. NTS based ISG aid in extending the drug release and thus display enhanced inhibitory effect on proliferation. 2. “Such antiproliferative action of RO could be attributed to its ability to down-regulate the expression of the DDX3 gene that plays a key role in cancer cell division.” This statement needs to have a citation. 3. What’s the rationale behind choosing Ellagic acid specifically over other natural anti-oxidant compounds? Specify that in the discussion or conclusion section. 4. There are a few typos in the manuscript that need to be corrected. 5. In figure 9, an important control (plain RO + EA) is lacking. 6. In the last paragraph of discussion, the authors mention Figure 11 Do they mean figure 9? 7. The two important experiments that make this story complete, but might be out of scope of this manuscript are the following. These points should be discussed in the discussion or conclusion section. a. Studying the in vivo behavior (pharmacokinetics) of RO-EA NTS-loaded ISG in cancer animal models. b. Doing permeability studies in human oral cancer tissues.