Mechanistic Toxicity of Fungal-Derived Silver-Containing Nanoparticles and Biochar: Redox and Inflammatory Responses in Breast and Colorectal Cancer Cells.

The present study was designed to assess the potential cytotoxic effects of fungal-mediated silver-containing nanoparticles (SNPs), alone and in combination with biochar, on breast and colon human cancer cells, with a special emphasis on inflammatory responses and redox status. Synthesis and characterization of SNPs were done via biosynthesis from Emericella dentata through XRD, FTIR, TEM, DLS, and zeta potential analysis. The cytotoxic effects were determined through MTT assay on cancer and normal HUVECs. Gene expression of pro-inflammatory cytokines such as TNFA, IL1β, and IL6, as well as antioxidants GPX and catalase, was studied by RT-PCR and ELISA. The X-ray diffraction result revealed that silver was present primarily in ionic form (AgNO3) instead of metallic Ag0, which suggested nanoparticle formation with bio-organic entities instead of metallic nanomaterials. The SNPs exhibited a mean hydrodynamic diameter of 149 nm (PDI = 0.133) and a zeta potential of -16.3 mV. There was dose-dependent toxicity toward the cells, and HCT116 cells were more susceptible compared to T-47D and HUVECs. There was moderate cytotoxicity from biochar, but when used together with SNPs, the effect increased. Dysregulation of genes related to inflammation and antioxidants was observed in the gene and protein profiling results. Docking did not show any receptor interaction. PPI and KEGG pathway analysis revealed TNFA, p53, NF-κB, and apoptosis pathways as critical regulators. The present study demonstrated that SNP-biochar formulations induce cytotoxic effects through a combination of inflammatory and redox status, rather than through direct interaction with inflammatory receptors.