Enantiomer-Dependent Biological Activity of Cysteine-Coated Ceria Nanoparticles in Colorectal Cancer Cells

Colorectal cancer (CRC) remains a major cause of cancer death, and advanced disease is still limited by resistance and systemic toxicity. We studied intrinsically active, biomimetic cerium oxide nanoparticles (CeNPs) functionalized with D- or L-cysteine (D-Cys@CeNPs and L-Cys@CeNPs) in three CRC cell lines (COLO-201, DLD-1, and LoVo) and healthy colon fibroblasts (CCD-18Co). We propose these materials act as enantioselective functional keys: cysteine stereochemistry shapes recognition at the nano–bio interface, while productive interactions allow the Ce³⁺-rich surface to drive localized redox exchange. We measured viability, ROS as a downstream phenotypic readout, Annexin V/PI-defined cell fate, and expression of the NF-κB regulatory genes TNFAIP3 (A20), IKBKG (NEMO), and NFKBIA (IκBα). Across the CRC panel, D-Cys@CeNPs caused earlier and stronger loss of viability, with the clearest effect in COLO-201, and shifted cells toward late apoptosis and necrosis. In contrast, L-Cys@CeNPs produced slower and more heterogeneous fate changes. Gene expression showed enantiomer-dependent differences in NF-κB feedback, consistent with differential pathway engagement. CCD-18Co fibroblasts were comparatively resistant to both enantiomers. Together, these findings link chiral CeNP surface design to redox-linked pathway regulation and support a materials-based route to selective anticancer activity.

INTRODUCTION