With nanotechnology's advancement and popularity, nanosafety assessment has attracted public attention, nanosafety assessment has attracted public attention. Silver nanoparticles (AgNPs) have been extensively applied in people’s work and life, but there is still limited knowledge of their potential toxicity to humans. Although many studies have shown that AgNPs causes physiological changes in the lung, the effects and molecular mechanisms of AgNPs on the lung are not fully understood at low-dose exposures and assessed with different physicochemical properties. To comprehensively compare the potential effects and molecular mechanisms of AgNPs with different particle sizes and surface modifications on A549 cells, three PVP-coated AgNPs with particle sizes of 20, 40, and 75 nm and Lipoic Acid (LA), mPEG, and BPEI-coated AgNPs with a particle size of 40 nm, which are referred to as PVP20, PVP40, PVP75, LA40, mPEG40 and BPEI40 were selected in this study. The methods used in this study included characterization of AgNP using transmission electron microscopy (TEM) and zeta potential, the study of cytotoxicity, oxidative stress, and subsequent damage to cell membrane integrity, apoptosis, and RNA-seq. Our findings indicated that AgNPs with different particle sizes and modifications had different toxicological effects, and the smaller size of AgNPs exerts the stronger cytotoxicity. In addition, transcriptome sequencing and qRT-PCR analyses confirmed that the mechanisms of action of these AgNPs varied, but PVP20, PVP40, PVP75, LA40, and BPEI40 AgNPs could all affect A549 cells via IL-17 signaling pathway. Our research findings demonstrate the deleterious effects of different nanosilvers on lung epithelial cells and reveal related possible pathways of influence.
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