Mitochondrial targeting and ROS modulation study by Trans-resveratrol loaded chitosan-coated green synthesized CeO₂ nanoparticles against Triple-negative breast cancer cell lines

Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive nature, absence of hormone receptors and limitation in therapeutic options. In this study, green-synthesized cerium oxide nanoparticles (CeO₂ NPs) were prepared using Moringa oleifera leaf extract, coated with chitosan (CS), and successfully encapsulated with trans-resveratrol (RSV) to enhance mitochondrial-targeted anticancer activity. Comprehensive characterization confirmed the formation of spherical nanoparticles with good colloidal stability, as revealed by XRD, UV–visible, FTIR, SEM, EDX, and zeta analysis. The RSV-CeO₂@CS nanoparticles selectively reduced the viability of MDA-MB-231 cells in dose dependent manner to 31.57 ± 2.08 % at 100 μg/mL. While RSV-CeO₂@CS exhibited significant biocompatibility toward normal MCF-10A cells with an IC₅₀ greater than 100 μg/mL. MitoTracker Red staining showed that RSV-CeO₂@CS effectively accumulated within mitochondria of TNBC cells. This targeted delivery led to enhanced generation of reactive oxygen species, as demonstrated by DCFH-DA assay, and triggered robust activation of caspase-9 and caspase-3 indicated the potential of the mitochondrial apoptotic pathway. The study highlights RSV-CeO₂@CS nanoparticles as a promising green nanoplatform for selective mitochondrial targeting and ROS-mediated apoptosis in TNBC therapy.