Breast cancer is the most common malignancy among women worldwide, with increasing incidence and significant mortality rates. Conventional treatment strategies, including chemotherapy and radiation, often lead to adverse side effects and may not effectively prevent cancer recurrence or metastasis. pH-sensitive nanoparticles offer a promising alternative, leveraging the acidic tumor microenvironment for targeted drug delivery with minimal systemic toxicity. This study investigates the therapeutic potential of pH-sensitive carvacrol-ZnO quantum dots (CVC-ZnO QDs) in a DMBA-induced mammary cancer model in female Sprague-Dawley rats. The study specifically examines the impact of CVC-ZnO QDs on protein-bound carbohydrate levels and the molecular regulation of Nrf-2, MAPK and NF-κB pathways. Four experimental groups were analyzed: a control group, a DMBA-induced cancer group, a CVC-ZnO QDs-alone treated group and a combined DMBA and CVC-ZnO QDs-treated group. Results revealed that DMBA-induced mammary cancer led to significant elevations in protein-bound carbohydrates, including hexose, hexosamine and sialic acid. CVC-ZnO QDs administration effectively restored these levels to near-normal concentrations. Immunohistochemistry, qRT-PCR and Western blot analyses demonstrated that CVC-ZnO QDs significantly downregulated MAPK and NF-κB expression while upregulating Nrf-2, suggesting enhanced antioxidant defense and suppression of tumor-promoting pathways. Molecular docking confirmed strong binding affinities of CVC to Nrf-2, MAPK and NF-κB, with key hydrogen bonding interactions contributing to the stability of ligand-protein complexes. These findings highlight the potential of CVC-ZnO QDs as a novel therapeutic strategy for breast cancer, offering targeted cytotoxicity with reduced systemic toxicity. Further studies are warranted to explore the clinical translatability of these nanocarriers in breast cancer treatment.
