Potential Immuno-therapeutic Role of Gold Nanoparticles on Toll-like Receptor Modulation in SKBR-3 Breast Cancer Cells

Abstract

Breast cancer is the most prevalent malignancy among women worldwide and is associated with high mortality rates in its metastatic stages. Emerging evidence highlights the role of Toll-like receptors (TLRs) in tumor progression, immune modulation, and chronic inflammation. Breast cancer remains the most commonly diagnosed malignancy among women globally and is a leading cause of cancer-related mortality, particularly in advanced metastatic stages. The complexity of breast cancer progression is increasingly attributed not only to genetic and hormonal factors but also to dysregulation of innate immune signaling pathways. Among these, (TLRs) Toll-like receptors are the class of pattern-recognition receptors, gained attention for their dual role in tumor promotion and immune activation. Recent studies have proposed TLRs as promising targets for therapeutic modulation, especially for tumor microenvironment remodeling. Gold nanoparticles (AuNPs) have emerged as highly versatile Nano-materials in cancer Nano-medicine due to their biocompatibility, tunable surface chemistry, and potential for drug delivery and immunomodulation. However, the interaction between AuNPs and TLR-mediated signaling pathways in breast cancer cells remains under-explored. This study aimed to investigate the impact of AuNPs on the expression patterns of key TLR genes in breast cancer cell line SKBR3, compared with the non-tumorigenic mammary epithelial cell line CRL-8798. Following treatment with citrate-stabilized AuNPs, total RNA was extracted and subject to qRT-PCR for the quantification of TLR gene-expression. Our results revealed that exposure to AuNPs significantly down-regulated the expression of TLR3, TLR8 and TLR9 in SKBR3 cells, suggesting the suppression of specific antiviral and pro-inflammatory pathways. Conversely, TLR1, TLR2 and TLR5 were markedly up-regulated, indicating a shift toward bacterial pattern recognition and potentially altered immune signaling dynamics. Interestingly, AuNP treatment also resulted in the up-regulation of p53, a pivotal tumor suppressor involved in apoptosis and cell cycle regulation, alongside the down-regulation of NF-κB, key transcription factor associated with inflammation, proliferation, and cancer progression. This reciprocal regulation suggests a possible crosstalk between the p53 and NF-κB pathways mediated by AuNP exposure. This comprehensive study demonstrates that gold nanoparticles can selectively modulate TLR expression and key oncogenic signaling pathways in breast cancer cells. These findings provide valuable insights into the potential of AuNPs as immuno-modulatory agents capable of influencing tumor-associated signaling cascades. These results will be helpful for future investigations into the therapeutic applications of nanoparticles in modulating innate immune responses in breast cancer and other malignancies.

Key Words: Breast cancer, AuNPs, SKBR3, CRL-8798, qRT-PCR, TLR3, TLR8, TLR9, TLR1, TLR2, TLR5, NF-κB, p53