| خلاصه مقاله | ERK1/ERK2 gene expression is often dysregulated in colorectal cancers (CRC), playing a critical role in its pathogenesis. This highlights this signaling pathway as a promising target for developing less toxic anticancer therapies. Advances in nanotechnology have enabled the creation of nanoscale devices functionalized with molecules like antibodies and enzymes. Given the overexpression of molecular markers such as EGFR in cancer cells, these can be exploited for targeted drug delivery. This study presents a novel CRC therapy using PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with Panitumumab, an FDA-approved anti-EGFR antibody, offering a targeted approach to treating metastatic CRC.
The SPIONs were synthesized and conjugated with Cet. The physicochemical properties of the engineered nano-biosystem (SPION-PEG-Cet) were characterized by UV-Vis spectrum, DLS, scanning electron microscope (SEM). The Anti-EGFR activity of the SPION-PEG-Cet was confirmed by western blotting. Then, its biological impacts, including cell viability and apoptosis (DAPI, Annexin-V), were evaluated in the colorectal cancer SW-480 cells. The apoptosis-related genes ERK1/2 expression were analyzed using real-time PCR.
The SEM results showed that the size of SPION-PEG-Cet was about 50 nm. The SPION-PEG-Cet nano-biosystem induced cytotoxicity and apoptosis in SW-480 cells. The maximum inducing apoptosis in SW-480 cells was obtained after treating cells with an IC50 dose of SPION-PEG-Cet. Besides, SPION-PEG-Cet was able to upregulate ERK1 and ERK2, indicating their key influence in the induction of apoptosis and overcoming resistance to Cet in KRAs mutant SW-480 cancer cells.
Our findings revealed that the engineered nano-biosystem could inhibit cell proliferation and induce apoptosis in CRC cells resistant to anti-EGFR monoclonal antibodies. Thus, the SPION-PEG-Cet nano-biosystem can be considered a novel treatment modality for CRC and other solid tu |