Postbiotic-assisted synthesis of cerium oxide nanocomposites functionalized with folic acid-chitosan and tea...

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of hormonal and HER2 receptors, which limits the effectiveness of conventional therapies. In this study, a multifunctional nanocomposite was developed by integrating cerium oxide nanoparticles (CeO₂ NPs) with bioactive and targeting components for selective TNBC treatment. CeO₂ NPs were synthesized using extracellular metabolites from Lactobacillus graminis, yielding uniformly dispersed and crystalline NPs. Tea polyphenols (TP) were subsequently loaded onto the CeO₂ NPs (5.07 ± 1.48 nm) to enhance redox functionality, followed by surface functionalization with folic acid-conjugated chitosan (FA-CS) to promote folate-assisted cellular uptake. The resulting FA-CS-LG-CeO₂-TP nanocomposite exhibited nanoscale uniformity in DLS (≈270 d.nm), near-neutral zeta potential, and good colloidal stability. FTIR and XRD analyses confirmed successful FA-CS functionalization without altering the crystalline structure of CeO₂. The nanocomposite showed sustained, pH-dependent TP release (≈63% at pH 5.4), strong antioxidant capacity in DPPH and ABTS assays, and good cytocompatibility in RAW 264.7 and NIH3T3 cells. Notably, FA-CS-LG-CeO₂-TP NCs induced significant cytotoxicity in MDA-MB-231 cells (≈60% reduction in viability) via ROS-mediated apoptosis, while maintaining minimal hemolytic activity (<4%). These findings demonstrate that postbiotic-mediated synthesis combined with polyphenol loading and FA-CS functionalization provides a promising nanoplatform for selective redox-regulated TNBC therapy.