Oxidative stress, including reactive oxygen species (ROS), has been known main cause of malignant disorders such as colorectal cancer (CRC). The nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. The current study introduced an effective nanomedicine composed of PEGylated super magnetic nanoparticles (SPIONs -PEG) conjugated with Cetuximab (Cet) that can induce ROSs mediating apoptosis pathways for CRC treatment.

The SPIONs are synthesized, stabilized by polyethylene glycol (PEG), functionalized, and covalently conjugated with Cet. The physicochemical properties of engineered nanomedicine (SPIONs -PEG-Cet) were characterized by UV-vis spectrum. Then, the impact of SPIONs -PEG-Cet on cell viability, ROS production, and oxidative stress gene expression (Kaep1- Nerf2) were evaluated in the CRC cell line.

The engineered nanomedicine effectively induced apoptosis in SW-480 cells and significantly reduced cancer cell viability. In addition, the maximum production of ROS was obtained after the treatment of cells with an IC50 dose of SPIONs-PEG-Cet. Based on real-time PCR data, in the treated SW-480 cells with the SPIONs -PEG-Cet, the expression level of Keap1 was significantly increased, while the expression of Nerf 2, were found to be significantly decreased as compared to the untreated control cells.

In the current study, we introduced a nanoformulation of Cet with a high apoptosis effect on CRC cells compared to the free Cet.