Electrophoresis-assisted accumulation of conductive nanoparticles for the enhancement of cell electropermeabilization.

The use of conductive nanoparticles (NPs) was previously proposed as a way to locally amplify the electric field (EF) intensity at the cell membrane to enhance cell electroporation. To achieve this, a close distance between the NPs and the cell membrane is mandatory. Here, a new method to improve the contact between NPs and cell surface using the effects of electric pulses (electrophoretic forces) is explored. The effects of two types of electric pulses are analyzed alone or combined in a two-pulse-train protocol on Chinese hamster DC-3F cells. Particularly we used 100 µs duration pulses, low intensity-millisecond pulses and combinations of both. Finally, we studied the use of surface coated NPs (PEGylated) for this application. Our results demonstrate that the delivery of an electric field prior to the electroporation pulses increases the accumulation of NPs around the cell membrane suggesting that NPs are pushed towards the cell surface through electrophoretic forces. This allowed reducing the need for long incubations between cells and NPs to observe an enhancement of electroporation mediated by conductive NPs. Thus low intensity-millisecond pulses can be used to increase the accumulation of either aggregated or individual (i.e. PEGylated) NPs supporting the electrophoretic nature of the observed effects.

Conductive nanoparticles improve cell electropermeabilization.

Conducive nanoparticles (NPs) were proposed to locally amplify the external electric field (EF) intensity at the cell surface to improve cell electroporation. To better understand the physical mechanisms behind this improvement, different types of NPs and several incubation conditions were applied to adherent cells in the present study. The enhancement of electroporation was observed in the presence of conductive NPs but not when non-conductive NPs were used. Experimental data demonstrate the influence of the incubation conditions between cells and NPs, which impact on the number and quality (aggregated or isolated) of the NPs surrounding the cells. While NPs can increase the number of electroporated cells, they have a more pronounced impact on the level permeabilization of each individual cell. Our results reveal the potential of conductive NPs to enhance the efficiency of electroporation via the amplification of the local EF at the cell surface as shown by numerical simulations.