Mechanistic Insights into the Anti-cancer Activity of Nanosulfur-Doped Zinc Oxide-Chitosan-PVA-PEG Nanocomposite in MDA-MB-231 Triple-Negative Breast Cancer Cells
摘要
Among various nanomaterials, nanocomposites are widely utilized in therapeutic applications due to their unique physical and chemical properties and biocompatibility. Polymeric nanocomposites, particularly those fabricated with chitosan, have gained significant attention in biomedicine as active bioactive agents. In this study, the anti-cancer activity of biogenic sulfur nanoparticle-zinc oxide nanoparticle-doped chitosan-polyvinyl alcohol-polyethylene glycol polymeric nanocomposites was investigated against breast cancer cells. The nanocomposite was fabricated by combining biogenic sulfur nanoparticles and chemogenic zinc oxide nanoparticles with a polymeric mixture of chitosan, polyvinyl alcohol, and polyethylene glycol, adopting the principles of in situ green chemistry. The structural and functional properties of the synthesized nanocomposite were analyzed using UV–visible absorption spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). These analyses revealed a highly stable, nanoscale polymeric-metal composite with marked crystallinity. The anti-cancer activity of the synthesized nanocomposite was evaluated against MDA-MB-231 triple-negative breast cancer cells using cell viability (cytotoxicity) assays, apoptosis induction, enzymatic antioxidant status, and in silico molecular docking studies. The nanocomposite demonstrated a dose-dependent cytotoxic effect. At a concentration of 9 µg/mL, the inhibition percentage was 46.26%, indicating significant cytotoxicity against the tested cancer cell line. The nanocomposite also exhibited notable apoptosis-inducing activity, with characteristic changes in antioxidant enzyme biomarkers. Further confirmation of the anti-cancer activity was obtained through in silico docking studies, where protein–ligand interactions were analyzed. Moesin, selected as the ligand, showed binding affinities of − 4.1 kcal/mol for PVA, − 2.7 kcal/mol for PEG, and − 9.3 kcal/mol for chitosan. This study suggests that the proposed polymeric nanocomposite could serve as an effective anti-cancer agent with high biocompatibility and efficacy.