Berry-derived gold nanoparticles induce integrated oxidative stress-mediated apoptosis, immune modulation, and transcriptomic remodeling in 4T1 triple-negative cancer cells

Key findings from differentially expressed gene enrichment analyses (GSEA) revealed positive gene enrichments of DNA repair regulators and TGF-β signaling while having negative enrichments of cell adhesion, cadherin and MAPK signaling via PI3K/AKT/MAPK/Wnt pathways, potentially influencing apoptosis and immune evasion intrinsic to cancer. Notably, decreased expression of PIK3CG, PALLD, PTPRZ1, and CDH8 and increased expression of SEMA6C, WWOX, NHEJ1, and MAML3 suggested suppression of epithelial-to-mesenchymal transition (EMT) and metastatic potential.

Further assessment of immunohistochemical, immunofluorescent, and flow cytometric data revealed that berry-derived nanoparticles can modulate oncogenic transcription factors and induce caspase-dependent execution-phase ROS-mediated apoptosis through pPAK1Thr212 dephosphorylation, downregulation of pPI3Kp85αγ(Tyr467/199)/pAKT1Thr450/mTOR signaling, and modulation of pJAK3Tyr785/STAT3 pathway supporting transcriptomic and transcriptional reprogramming of 4T1 treated cells.

Together, our findings uncover a new strategy to capture berry-derived polyphenols required to regulate apoptosis, autophagy, immune response, and metastasis-related gene networks in breast cancer thereby underscoring the therapeutic potential of functionalized AuNPs as delivery platforms for dietary phytochemicals.