Gold nanoparticles mediate suppression of angiogenesis and breast cancer growth via MMP-9/NF-κB/mTOR and PD-L1/PD-1 signaling: integrative in vitro validation and network pharmacology insights

Gold nanoparticles (AuNPs) have emerged as promising candidates for cancer therapy due to their unique physicochemical properties and biocompatibility. In this study, we investigate the synthesis, characterization, and therapeutic potential of AuNPs in breast cancer treatment. Further, it establishes a comprehensive understanding of the mechanisms by which AuNPs suppress angiogenesis and breast cancer growth, identifying novel targets and signaling nodes contributing to the anti-tumor effects of AuNPs. AuNPs were synthesized and characterized using UV-Vis, crystallography, transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The cytotoxicity of AuNPs was evaluated in WI-38 normal cells and MCF-7 breast cancer cells using the MTT assay. Additionally, the antioxidant activity of AuNPs was assessed through free radical scavenging and lipid peroxidation inhibition assays. Gene expression and pathway enrichment analyses were performed to elucidate the molecular mechanisms underlying the therapeutic effects of AuNPs in breast cancer. UV-Vis spectroscopy confirmed the successful synthesis of AuNPs, with a strong peak observed at 488.9 nm. Crystallography and TEM analysis revealed the crystalline nature and uniform size distribution of AuNPs, respectively. AuNPs exhibited concentration-dependent cytotoxic effects on MCF-7 cells, significantly inhibiting cancer cell proliferation at lower concentrations. Moreover, AuNPs demonstrated potent antioxidant activity, surpassing the effectiveness of vitamin C in scavenging free radicals and inhibiting lipid peroxidation. Gene expression analysis revealed modulation of crucial cancer-related genes and signaling pathways, including MMP-9/NF-κB/mTOR, PD-L1 expression and PD-1 checkpoint pathway, TNF signaling pathway, and adipocytokine signaling pathway, suggesting their potential as novel therapeutics for breast cancer treatment. Our findings support the promising role of AuNPs as effective and targeted therapeutics for breast cancer treatment. Further research is warranted to elucidate the precise mechanisms of action and evaluate the clinical efficacy and safety of AuNP-based therapies in breast cancer patients.