Probiotic-derived EPS-ZnO nanoparticles: therapeutic potential in colorectal cancer gene regulation

Colorectal cancer (CRC), the third most common and second deadliest cancer worldwide, arises from the abnormal growth of epithelial cells in the colon or rectum. This study focused on the oncogenes BCL9, KRAS, and WNT10A, alongside the tumor suppressor genes PDCD4, PTEN, and LRIG3, in the SW480 cell line. Probiotics, valued for their antioxidant and anti-cancer effects—especially due to their exopolysaccharides (EPS)—are promising in cancer prevention. Nanoparticles (NPs) hold great potential for diagnosing and treating various diseases, including cancer. Among them, zinc oxide NPs (ZnONPs) stand out for their unique physical and chemical properties, making them widely used in drug delivery, cancer diagnosis, and therapy. In this study, EPS were extracted and purified from the probiotic bacterium Lactiplantibacillus plantarum at a concentration of 301 ± 0.12 mg/L, and subsequently employed in the biosynthesis of ZnONPs, achieving an optimal yield of approximately 61.2%. Validation tests (UV-Vis, XRD, FTIR, FE-SEM, TEM, and zeta potential analysis) were conducted on the ZnONPs coated with exopolysaccharide (EPS-ZnONPs). The cytotoxicity of EPS and EPS-ZnONPs was assessed on the SW480 cell line, and their antioxidant properties were evaluated. Quantitative cycle variations (∆∆Cqs) measured via the Real-time PCR system, following the treatment of the cancerous cell line with the target metabolites, demonstrated reduced expression of oncogenes and increased expression of tumor suppressors. The results indicated that EPS extracted from probiotics, as well as EPS-ZnONPs, could serve as effective agents in the treatment of CRC by modulating the expression levels of genes involved in the development of this cancer.