Selective Targeting of Neurons with Inorganic Nanoparticles: Revealing the Crucial Role of Nanoparticle Surface Charge

Nanoparticles
(NPs) are increasingly used in biomedical applications,
but the factors that influence their interactions with living cells
need to be elucidated. Here, we reveal the role of NP surface charge
in determining their neuronal interactions and electrical responses.
We discovered that negatively charged NPs administered at low concentration
(10 nM) interact with the neuronal membrane and at the synaptic cleft,
whereas positively and neutrally charged NPs never localize on neurons.
This effect is shape and material independent. The presence of negatively
charged NPs on neuronal cell membranes influences the excitability
of neurons by causing an increase in the amplitude and frequency of
spontaneous postsynaptic currents at the single cell level and an
increase of both the spiking activity and synchronous firing at neural
network level. The negatively charged NPs exclusively bind to excitable
neuronal cells, and never to nonexcitable glial cells. This specific
interaction was also confirmed by manipulating the electrophysiological
activity of neuronal cells. Indeed, the interaction of negatively
charged NPs with neurons is either promoted or hindered by pharmacological
suppression or enhancement of the neuronal activity with tetrodotoxin
or bicuculline, respectively. We further support our main experimental
conclusions by using numerical simulations. This study demonstrates
that negatively charged NPs modulate the excitability of neurons,
revealing the potential use of NPs for controlling neuron activity.