SiO2 nanoparticles modulate the electrical activity of neuroendocrine cells without exerting genomic effects (original) (raw)

Engineered silica nanoparticles (NPs) have attracted increasing interest in several applications, and particularly in the field of nanomedicine, thanks to the high biocompatibility of this material. For their optimal and controlled use, the understanding of the mechanisms elicited by their interaction with the biological target is a prerequisite, especially when dealing with cells particularly vulnerable to environmental stimuli like neurons. Here we have combined different electrophysiological approaches (both at the single cell and at the population level) with a genomic screening in order to analyze, in GT1-7 neuroendocrine cells, the impact of SiO 2 NPs (50 ± 3 nm in diameter) on electrical activity and gene expression, providing a detailed analysis of the impact of a nanoparticle on neuronal excitability. We find that 20 µg mL −1 NPs induce depolarization of the membrane potential, with a modulation of the firing of action potentials. Recordings of electrical activity with multielectrode arrays provide further evidence that the NPs evoke a temporary increase in firing frequency, without affecting the functional behavior on a time scale of hours. Finally, NPs incubation up to 24 hours does not induce any change in gene expression. The fast development of nanoparticles (NPs) designed and engineered to be employed as tools for targeting to specific cells and tissues and for drug delivery has opened an entire new field in both basic science and medical applications. A preliminary, albeit essential, phase was devoted at addressing the concerns about their potential toxicity in vitro and, more relevantly, in vivo. A huge amount of papers 1-3 has evidenced the parameters (size, concentration, surface properties, etc.) that can determine the presence or absence of toxic effects, thus providing the rational background for designing safe and biocompatible nanotools. The next step is to switch the focus on the more subtle effects that can arise from a prolonged presence of NPs in contact with cells, and to understand the mechanisms that underlie the interaction between objects at the nanoscale and their cellular and molecular targets. This task is particularly relevant when the target is represented by single nerve cells or by complex neuronal networks. Engineered silica NPs have encountered a rapid diffusion in several applications in the last decade 4 , specifically in nanomedicine, thanks to the high biocompatibility of this material 5. We have reported that amorphous 50 nm SiO 2 NPs can be made fluorescent by hybridization with cyanine dyes and can be safely incorporated into neurons 6 and other cell types 7. In a previous paper, we have shown that 50 nm SiO 2 NPs, at non-toxic doses, elicit increases in the intracellular calcium concentration, [Ca 2+ ] i , in a neuroendocrine cell line, GT1-7 cells 8. These signals are fully dependent on calcium influx, carried through different types of calcium permeable channels, and are completely reversible even in the continuous presence of NPs. A few other papers 3,9-11 have reported that NPs of different composition can elicit changes in neuronal [Ca 2+ ] i. This is a relevant topic, since perturbations of