Generic prediction of exocytosis rate constants by size-based surface energies of nanoparticles and cells

Nanotechnology brings benefits in fields such as biomedicine but nanoparticles (NPs) may also have adverse health effects. The effects of surface-modified NPs at the cellular level have major implications for both medicine and toxicology. Semi-empirical and mechanism-based models aid to understand the cellular transport of various NPs and its implications for quantitatively biological exposure while avoiding large-scale experiments. We hypothesized relationships between NPs-cellular elimination, surface functionality and elimination pathways by cells. Surface free energy components were used to characterize the transport of NPs onto membranes and with lipid vesicles, covering both influences by size and hydrophobicity of NPs. The model was built based on properties of neutral NPs and cells, defining Van de Waals forces, electrostatic forces and Lewis acid–base (polar) interactions between NPs and vesicles as well as between vesicles and cell membranes. We yielded a generic model for estimating exocytosis rate constants of various neutral NPs by cells based on the vesicle-transported exocytosis pathways. Our results indicate that most models are well fitted (R(2) ranging from 0.61 to 0.98) and may provide good predictions of exocytosis rate constants for NPs with differing surface functionalities (prediction errors are within 2 times for macrophages). Exocytosis rates differ between cancerous cells with metastatic potential and non-cancerous cells. Our model provides a reference for cellular elimination of NPs, and intends for medical applications and risk assessment.