Nanotechnology is an emerging scientific area that has created a multiplicity of versatile submicrometersized materials. Different types of nanoparticles (NPs) have been developed with peculiar physicochemical properties (such as chemical reactivity, energy absorption and biological mobility) that are not present when the same materials are analyzed at a micro-macroscopic scale. This behavior has made them central components in an array of emerging technologies, from medical applications to environmental sciences. Among other nanomaterials, silica nanoparticles (SiO2 NPs) are considered highly biocompatible and easily internalized into the cells. The ability to cross biological barriers has made them potential tools in pharmaceutical and biomedical research, with various applications ranging from contrast agents in molecular imaging to carriers for drug delivery systems. Notwithstanding the increasing number of toxicological studies on SiO2 NPs, our knowledge of the cellular responses induced by their interaction with cells is still incomplete. The internalization of NPs can affect many functional parameters interfering with the biological procesess of the cells. Because of the great relevance of intracellular calcium concentration as a critical parameter controlling both physiological and pathological processes, mainly in neuronal cells, calcium homeostasis is one of the key players. The impact of NPs on neuronal calcium homeostasis has been investigated in the GT1-7 neuronal line. The preliminary data obtained by means of a calcium imaging approach provided the evidence of strong, long lasting and reversible responses following the interaction of NPs administered at non toxic concentration. Evidence has been provided for a localization of the interaction at the plasmamembrane. Since the calcium imaging approach provides only an indirect information about the molecular identity of the channels targeted by the NPs, we used the patch clamp technique to obtain more direct and quantitative information. On the basis of the data obtained we provide a preliminary identification of some candidate channels for the responses observed. The interaction between nanoparticles and cells can not only perturbate cytosolic calcium homeostasis but also induce reactive oxygen species (ROS) formation. Since these two mechanism are closely related, with calcium signals placed either upstream or downstream of ROS production, we investigated a possible involvement of free radicals in the activation of membrane channels. NAC (N-acetylcysteine) antioxidant was used to detect this potential indirect pathway of channel's activation elicited by NPs.

Le correnti ioniche generate dall'interazione con le nanoparticelle di silice, nella linea cellulare GT1-7

DIONISI, MARIANNA
2014/2015

Abstract

Nanotechnology is an emerging scientific area that has created a multiplicity of versatile submicrometersized materials. Different types of nanoparticles (NPs) have been developed with peculiar physicochemical properties (such as chemical reactivity, energy absorption and biological mobility) that are not present when the same materials are analyzed at a micro-macroscopic scale. This behavior has made them central components in an array of emerging technologies, from medical applications to environmental sciences. Among other nanomaterials, silica nanoparticles (SiO2 NPs) are considered highly biocompatible and easily internalized into the cells. The ability to cross biological barriers has made them potential tools in pharmaceutical and biomedical research, with various applications ranging from contrast agents in molecular imaging to carriers for drug delivery systems. Notwithstanding the increasing number of toxicological studies on SiO2 NPs, our knowledge of the cellular responses induced by their interaction with cells is still incomplete. The internalization of NPs can affect many functional parameters interfering with the biological procesess of the cells. Because of the great relevance of intracellular calcium concentration as a critical parameter controlling both physiological and pathological processes, mainly in neuronal cells, calcium homeostasis is one of the key players. The impact of NPs on neuronal calcium homeostasis has been investigated in the GT1-7 neuronal line. The preliminary data obtained by means of a calcium imaging approach provided the evidence of strong, long lasting and reversible responses following the interaction of NPs administered at non toxic concentration. Evidence has been provided for a localization of the interaction at the plasmamembrane. Since the calcium imaging approach provides only an indirect information about the molecular identity of the channels targeted by the NPs, we used the patch clamp technique to obtain more direct and quantitative information. On the basis of the data obtained we provide a preliminary identification of some candidate channels for the responses observed. The interaction between nanoparticles and cells can not only perturbate cytosolic calcium homeostasis but also induce reactive oxygen species (ROS) formation. Since these two mechanism are closely related, with calcium signals placed either upstream or downstream of ROS production, we investigated a possible involvement of free radicals in the activation of membrane channels. NAC (N-acetylcysteine) antioxidant was used to detect this potential indirect pathway of channel's activation elicited by NPs.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14240/159002