Abstract Background Today, cosmetic products are very popular with both men and women to improve their appearance and increase their social acceptability. Results In this study, nano-sized (30–300 nm) plastic particles were isolated from the commercial face-scrubs and treated on the human keratinocytes. The observed adherence of polyethylene nano-plastics (PENPs), polystyrene NPs (PSNPs), and face-scrubs isolated nano-plastics (NPs) on the keratin layer reveals a significant attachment of NPs from the cosmetics that are applied on the skin for a short duration. This attachment property could facilitate further adherence of protein molecules on NPs and the protein-corona formation. The protein-corona mimics protein aggregates, thereby triggers macropinocytosis, followed by the macropinolysosomal process in the cell. These internalized NPs induced the concentration-dependent cytotoxic, cytostatic and cytoprotective activity in keratinocytes. Both single dose and chronic long-term exposure of lethal and sub-lethal concentrations of NPs resulted in oxidative stress-mediated down-regulation of cell growth and proliferation inhibition. Autophagic structures and premature aging were also observed using an electron microscopy and a senescence marker, respectively in the NPs internalized HaCaT cells incubated in a fresh, NPs-free medium. Conclusion Though 2D culture models have many limitations, it produces significant conceptual advancements. This work provides an insight into the NPs concentration-dependent regulatory, cytoprotective, and cytotoxic effects in HaCaT cells. However, 3D model studies are required to identify the detailed mechanisms of NPs toxicity and cytoprotective events in cells at the molecular level. Graphic abstract
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