Nanoparticles are considered a primary vehicle for targeted therapies because they can pass biological barriers and enter and distribute within cells by energy-dependent pathways. So far, most studies have shown that nanoparticle properties, such as size and surface, can influence how cells internalize nanoparticles. Here, we show that uptake of nanoparticles by cells is also influenced by their cell cycle phase. Although cells in different phases of the cell cycle were found to internalize nanoparticles at similar rates, after 24 h the concentration of nanoparticles in the cells could be ranked according to the different phases: G2/M > S > G0/G1. Nanoparticles that are internalized by cells are not exported from cells but are split between daughter cells when the parent cell divides. Our results suggest that future studies on nanoparticle uptake should consider the cell cycle, because, in a cell population, the dose of internalized nanoparticles in each cell varies as the cell advances through the cell cycle.

Nanomaterials challenge paradigms of in vitro testing because unlike molecular species, biomolecules in the dispersion medium modulate their interactions with cells. Exposing cells to nanoparticles known to cause cell death, we observed cytotoxicity suppression by increasing the amount of serum in the dispersion medium towards in vivo-relevant conditions.

The interaction of nanoscaled materials with biological systems is currently the focus of a fast-growing area of investigation. Though many nanoparticles interact with cells without acute toxic responses, amino-modified polystyrene nanoparticles are known to induce cell death. We have found that by lowering their dose, cell death remains low for several days while, interestingly, cell cycle progression is arrested. In this scenario, nanoparticle uptake, which we have recently shown to be affected by cell cycle progression, develops differently over time due to the absence of cell division. This suggests that the same nanoparticles can trigger different pathways depending on exposure conditions and the dose accumulated.

-Nano-sized objects interact with biological systems in fundamentally novel ways, thereby holding great promise for targeted drug-delivery. It has also been suggested they could constitute a hitherto unseen hazard. Numerous experimental studies in the field are taking place. We consider that the nature of the interactions allows a more fundamental theoretical framework to be developed. In particular, we describe the intimate link that develops between nanoparticle uptake and cell population evolution. Explicit analytical results are given and the theory compared to experimental observations.

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