Investigating the effects of cetuximab conjugated to supermagnet on oxidative stress and apoptosis of colorectal cancer cells

Abstract

Background:Colorectal cancer (CRC) is a prevalent and lethal form of cancer. Reactive oxygen species (ROS) are thought to play a significant role in CRC development. Cetuximab(Cet) is an antibody used in CRC treatment that targets the epidermal growth factor receptor(EGFR). However, its effectiveness is limited by the emergence of resistance mechanisms. To address this, PEGylated Fe3O4 nanoparticles(SPIONs) conjugated with cetuximab(EMNP-PEG-Cet) were developed in this study. Purpose::In this study is to develop and synthesize a targeted nano-drug to overcome drug resistance in colorectal cancer cells with mutations in the KRAS gene. The nano-drug's effectiveness will be evaluated against the chemotherapy drug cetuximab, and its impact on oxidative stress and apoptosis will be investigated in SW480 cells.Methods:A targeted nano-drug based on PEGylated Fe3O4 nanoparticles conjugated with cetuximab was successfully synthesized, and its physicochemical properties were characterized. The cytotoxic effects of this nano-drug on SW480 cells were assessed using the MTT assay. Additionally, its impact on apoptosis and nuclear morphological changes was investigated using techniques such as MTT assay, flow cytometry, DAPI and DCHF2 staining. The effects on cell apoptosis were analyzed using annexin-V. Furthermore, the nano-drug's influence on oxidative stress was examined through DCHF2 staining, employing fluorescence microscopy and flow cytometry techniques. Results :The study revealed the cytotoxic effects of the targeted nanostructure against SW480 cells and its ability to overcome drug resistance in this cell line. The EMNP-PEG-Cet nanoconjugates suppressed the growth of KRAS mutant SW-480(G12V) cells by inducing apoptosis through ROS production mediation.Conclusion:This investigation presents an efficient nanobiosystem (EMNP-PEG-Cet) that has the potential to enhance the anticancer efficacy of cetuximab in KRAS mutant SW480 CRC cells by mediating ROS production and inducing apoptosis.