Postbiotic-assisted synthesis of cerium oxide nanocomposites functionalized with folic acid-chitosan and tea polyphenols for redox-regulated anticancer activity

초록

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 (approximate to 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 (approximate to 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 (approximate to 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.

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