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Mechanistic Toxicity of Fungal-Derived Silver-Containing Nanoparticles and Biochar: Redox and Inflammatory Responses
Moath Alqaraleh1, Futoon Abedrabbu Al-Rawashde1, Ali Al-Samydai2
1Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Balqa Applied University, Salt, Jordan.
Abstract:
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.
Insights
Fungal-mediated silver nanoparticles (SNPs) combined with biochar show dose-dependent cytotoxicity against breast and colon cancer cells. This effect is linked to inflammatory and redox status changes, not direct receptor interaction.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Cancer Research
Background:
- Silver nanoparticles (SNPs) are explored for cancer therapy.
- The role of biochar in nanoparticle-based cancer treatment is under investigation.
- Understanding the impact on inflammatory and redox pathways is crucial for novel therapeutic strategies.
Purpose of the Study:
- To evaluate the cytotoxic effects of fungal-mediated SNPs, alone and with biochar, on human breast (T-47D) and colon (HCT116) cancer cells.
- To investigate the influence of these formulations on inflammatory responses and cellular redox status.
- To elucidate the underlying molecular mechanisms, including gene expression and pathway analysis.
Main Methods:
- Biosynthesis and characterization of SNPs using *Emericella dentata* (XRD, FTIR, TEM, DLS, zeta potential).
- Cytotoxicity assessment via MTT assay on cancer cells and normal HUVECs.
- Analysis of pro-inflammatory cytokines (TNFA, IL1β, IL6) and antioxidant gene expression (GPX, catalase) using RT-PCR and ELISA.
- Bioinformatic analysis including docking, PPI, and KEGG pathway analysis.
Main Results:
- SNPs were primarily ionic (AgNO3) with bio-organic entities, exhibiting a mean size of 149 nm and zeta potential of -16.3 mV.
- Dose-dependent cytotoxicity observed, with HCT116 cells being more susceptible than T-47D and HUVECs.
- Combined SNP-biochar formulations enhanced cytotoxicity compared to individual components.
- Gene and protein profiling revealed dysregulation of inflammatory and antioxidant pathways, with TNFA, p53, NF-κB, and apoptosis pathways identified as critical regulators.
Conclusions:
- Fungal-mediated SNP-biochar formulations exhibit significant dose-dependent cytotoxicity against breast and colon cancer cells.
- The cytotoxic mechanism involves the modulation of inflammatory and redox status, rather than direct receptor binding.
- These findings suggest potential for SNP-biochar composites as a novel strategy in cancer therapy, warranting further investigation.
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