Action Potentials as a Mean to Trigger the Specific Interaction of Negatively Charged Nanoparticles with Electrically Excitable Cells.

In this study, we dig to understand the nanoparticle (NP)–cell interaction and the roles of the NP surface charge and the cell membrane potential. While the interaction between negatively charged cadmium selenide/cadmium sulfide (CdSe/CdS) NPs and primary neurons was determined in our previous study, here, by using differentiated mouse neuroblastoma (N2a) cells, nondifferentiated N2a cells, and Chinese hamster ovary (CHO) cells, we are able to understand the relation between electrically excitable cells and non-excitable cells with the same type of NPs in a more systematic way. Indeed, we demonstrate that highly negatively charged CdSe/CdS NPs (−50 mV) interact with the cell membrane of electrically active cells, such as those of primary neurons and differentiated N2a cells, while no interaction occurs with non-electrically active cells, such as CHO cells and nondifferentiated N2a cells. Notably, by ad hoc designed patch-clamp experiments, we confirm that the interaction of the negatively charged NPs with neuronal cells is triggered by the membrane electrical activity. In contrast, no interaction with the cellular membrane is noted in the control unstimulated patch-clamp neuronal cells performed with NPs bearing an almost neutral charge. Furthermore, we show that the interaction between electrically excitable cells occurs with NPs independently of their inorganic nature. Indeed, by replacing the inorganic rod-shaped NPs with negatively charged polymeric micelles made of the same polymer used for the CdSe/CdS NPs surface coating but without the inorganic core (CdSe/CdS NPs), the cell surface interaction still occurs with neuronal excitable cells. These data suggest that, independent of the organic or inorganic nature of the NPs tested here, the specificity of the NP–cell membrane interaction is still affected by the electric activity of the neuronal cells when negatively charged nanoplatforms are used. [ABSTRACT FROM AUTHOR]