Size-dependent cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles toward HeLa cells.

In this study, we investigated and reported the cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles (SNPs) with different sizes. Using confocal laser scanning microscope (CLSM), flow cytometry (FCM), and graphite furnace atomic absorption spectrometry (GFAAS), the qualitative and quantitative experimental results showed that the cellular uptake of SNPs toward HeLa cells is size-dependent. To further examine the uptake process, three different inhibitors including sucrose, Filipin III, and Cytochalasin D (Cyt D) were introduced to pretreat the HeLa cells. It appeared that the largest SNPs (SNPs-307.6) take an energy-dependent uptake pathway (clathrin dependent and caveolin independent) while that for the medium size SNPs-167.8 involves clathrin and caveolin dependent endocytosis. In contrast, the smallest SNPs (SNPs-55.6) follow not only energy required clathrin and caveolin dependent endocytosis but also an energy independent pathway to efficiently enter the cells. Moreover, the cellular uptake efficiency of SNPs, which also show excellent biocompatibility, is size-dependent in the order of 55.6>167.8>307.6 nm. This knowledge is fundamentally important and will facilitate more development of size-defined SNPs as the transporters for various purposes.