Molecular insights into the anti-cancer activity of chitosan-okra mucilage polymeric nanocomposite doped with nano zero-valent iron against multi-drug-resistant oral carcinoma cells

Int J Biol Macromol. 2024 Dec 6:286:138495. doi: 10.1016/j.ijbiomac.2024.138495. Online ahead of print.

Abstract

Recent advances in nanotechnology, particularly those utilizing polymeric nanocomposites, have garnered significant attention for their effectiveness and biocompatibility in cancer diagnosis and treatment. In this study, a chitosan-okra mucilage polymeric nanocomposite doped with nano zero-valent iron (CS-OM-nZVI), synthesized using green chemistry principles, was evaluated for its anti-cancer activity against drug-resistant oral carcinoma cells (KBChR). The nanocomposite was created from chitosan, mucilage derived from okra biomass, and nano zerovalent iron particles synthesized through chemical reduction. The resulting nanocomposite exhibited a highly stable, crystalline nanoscale structure with excellent stability. Anti-cancer activity was assessed by measuring cell viability, apoptosis induction, oxidative stress markers, DNA fragmentation, and performing in silico docking studies between the components of the polymeric nanocomposite (CS-OM-nZVI) and key proteins involved in carcinoma pathogenesis. The nanocomposite demonstrated significant anticancer activity, with an IC50 of 600 μg/mL, indicating notable effects on cell viability. It also induced significant morphological changes associated with apoptosis, such as chromatin condensation and nuclear fragmentation. Additionally, the nanocomposite had a marked effect on oxidative stress markers, particularly catalase and superoxide dismutase activity. In silico docking studies revealed that the polymeric composite modulates and enhances both intrinsic and extrinsic apoptotic pathways, confirmed by chitosan's binding to Caspase-3. This study suggests that the prepared nanocomposite is a promising anti-cancer agent against drug-resistant oral carcinoma cells, demonstrating a significant impact on cancer cell viability.

Keywords: Anticancer; Caspase 3; Chitosan; Mucilage; Oral carcinoma; Polymeric nanocomposite.