Silver and polystyrene nanoparticles activate oestrogen signalling via cytoplasmic oestrogen receptor

This study explores the endocrine-disrupting potential of two commonly encountered nanomaterials, nanoplastic and silver nanoparticles (AgNPs). Many environmental pollutants, especially endocrine-disrupting chemicals (EDCs), such as bisphenol, heavy metals, interfere with hormone function, posing a serious risk for public health, e.g. prevalence of breast cancer, whose incidence correlates strongly with EDC exposure. However, the impact on hormonal homeostasis of many environmental contaminants, such as nanoplastic, is still unknown. Nanoplastic is a product of the weathering process of plastic goods, while AgNPs are released to the environment from everyday use items, such as health care products, food-related materials or medical devices. These nanoparticles penetrate biological barriers, accumulate in tissues, and may affect oestrogen signalling. Thus, this study investigated how AgNPs and nanopolystyrene (PSNPs) interact with oestrogen receptor (ESR1) signalling in breast cancer cells. The study revealed that in ESR1-positive (ER+) cells, AgNPs notably enhanced ESR1-mediated cell proliferation and progression through the S-phase of the cell cycle, particularly in oestrogen-deprived conditions. The observed effect was ESR1-dependent and effectively blocked by tamoxifen, revealing a ligand-independent activation mechanism. AgNPs downregulated ESR1 signalling-dependent genes, which are linked to cell cycle and proliferation pathways (e.g., IRS1, NCOR1, MED1). PSNPs showed a similar, but milder effect, stimulating ESR1 activation only in the presence of oestrogen (E2). Simultaneous treatment with AgNPs and PSNPs induced a distinct effect, namely, reduced CITED2 and BDNF expression, which was highly dependent on E2 status. The presence of PSNPs also mitigated AgNPs-induced reduction of BRCA1 expression. This study highlights how nanomaterial-induced ESR1 activation can lead to enhanced epithelial-mesenchymal transition and cell cycle progression, suggesting potential adverse effects of nanomaterials in ER+ cancer proliferation via protein kinase-mediated ESR1 modulation.