Cell-excreted proteins mediate the interactions of differently sized silica nanoparticles during cellular uptake

Exposure to different types of nanoparticles (NPs) results in their deposition in human bodies. While most studies have examined the cellular uptake of only one type of NP at a time, how the dynamics of NP uptake may change in the presence of other types of NPs remains unclear. We therefore investigated the interplay of two differently sized SiO₂ NPs during their uptake by A549 human lung carcinoma cells. Both NPs contained a CdSeTe core, which was labeled with different Cd isotopes to differentiate between them. Our study showed that the uptake of one size of SiO₂ NPs either increased or decreased with the concentration of the other size of SiO₂ NPs. This variation in uptake was attributable to the concentration-dependent aggregation of SiO₂ NPs, as determined by the amount of cell-excreted proteins adsorbed on the NP surface. Further, the effects of the protein corona on the attachment of SiO₂ NPs to the cell surface and uptake competition between differently sized SiO₂ NPs also played important roles. Cell-excreted proteins were then analyzed by proteomics. Overall, the complex interactions between coexisting NPs of different physicochemical properties and cell-excreted proteins should be considered during bio-applications and bio-safety evaluations of NPs.