Synthesis of a nano-emulsion of quercetin encapsulated vitamin E conjugated iron oxide nanoparticles for the systemic phyto-preventive effect: characterization and oral cancer application

<i>Background</i>: Globally, one of the most pressing public health concerns is the prevention of oral cancerous lesions. This study aimed to reverse the carcinogenic effect of DMBA in hamsters by using nano-emulsions of quercetin encapsulated vitamin E and iron oxide. <i>Methods:</i> The studied iron oxide nanoparticles were prepared by the co-precipitation method and then converted into nano-emulsions <i>via</i> the oil-in-water technique and characterized. The study included five equal groups of 30 Syrian male hamsters aged eight weeks. Group A constituted a negative control, and Group B received 25 mg kg^-1 of nano-emulsion orally three times per week for eight weeks. Group C (positive control) was painted with DMBA on the left pouches three times per week for six weeks. Group D received 25 mg kg^-1 of quercetin thrice per week for two weeks orally, with a continued painting of DMBA per week for six weeks. Group E received 25 mg kg^-1 of nano-emulsion orally, three times per week, for two weeks, and then continued using it with painting DMBA three times per week for six weeks. <i>Results</i>: The morphological and chemical characterization of the synthesized emulsions revealed the formation of spherical particles in the nanoscale emulsion. A significant improvement was noted in the nano-emulsion group compared to the DMBA-painted group in multiple biochemical parameters, such as hemoglobin, RBCs, platelets, WBCs, neutrophils, lymphocytes, monocytes, ALT, AST, creatinine, and urea. The histopathological and immunohistochemical assessments revealed well-differentiated squamous cell carcinoma in the DMBA-treated group, with intense expression of Ki-67 and Bcl-2. In the quercetin-treated group, superficial invasion of carcinoma <i>in situ</i> was noted with a moderate decrease in the expression of Ki-67 and Bcl-2. Marked improvement was observed in the quercetin nano-emulsion-treated group that showed moderate to severe dysplasia with an obvious decrease in Ki-67 and Bcl-2 expression. <i>Conclusion</i>: The study results confirmed that the prepared quercetin-vitamin E-Fe₃O₄ formulations are novel in combining magnetic targeting and antioxidant co-protection nano-emulsions and significantly prevented oral squamous cell carcinoma in hamsters.