Unveiling the Potential Therapeutic Efficacy of Gold Ceria Nanohybrid as an Anticancer Agent: A Special Insight to Molecular Docking Study

Over the last decades, nanoformulations embody a versatile and highly promising approach in cancer therapeutics by enabling targeted, controlled, and multimodal treatment strategies. To copiously comprehend their clinical potential, further research, standardization, and toxicological assessment are essential. A green synthetic approach was employed to develop gold-core cerium oxide-shell (Au/CeO2) nanohybrid with enhanced anticancer properties. Comprehensive physicochemical characterization confirmed successful nanoparticle formation. Improved cellular uptake of Au/CeO2 nanoparticles in MDA-MB-231 triple-negative breast cancer (TNBC) cells was attributed to enhanced permeability and retention (EPR) effects and gold-mediated synergistic internalization. JC-1 staining indicated significant mitochondrial membrane depolarization following treatment, suggesting induction of apoptosis via mitochondrial dysfunction. The micrographs were also validated; scanning electron microscopy and phalloidin staining revealed disrupted cytoskeletal architecture, correlating with reduced cellular migration. Western blot analysis showed suppression of nuclear NFκB-p65 expression, upregulation of PTEN, and downregulation of pAKT (Ser473), implicating nanoparticle-mediated modulation of the NFκB/PTEN/pAKT signaling axis. Henceforth, molecular docking studies further supported these findings, revealing favorable binding of Au/CeO2 nanocargo and 5-fluorouracil to cancer-associated targets such as p53, NFκB, and kinase proteins. Ramachandran plot analyses validated the structural integrity of the selected target proteins. Finally, in vivo cytotoxicity profiling of the Au/CeO2 nanohybrid under control and LPS-treated conditions not only validates the non-toxic nature but also intimates its anti-inflammatory potency indicating a distinctive avenue for further investigations. Concomitantly, these findings highlight the potential of Au-CeO2 nanoparticles as a multifunctional nanoplatform for targeted cancer therapy through synergistic cellular uptake, apoptotic induction, and signaling pathway modulation in aggressive TNBC models.