Abstract
Platinum nanoparticles (PtNPs) have unique physico-chemical properties that led to their use in many branches of medicine. Recently, PtNPs gathered growing interest as delivery vectors for drugs, biosensors and as surface coating on chronically implanted biomedical devices for improving electrochemical properties. However, there are contradictory statements about their biocompatibility and impact on target organs such as the brain tissue, where these NPs are finding many applications. Furthermore, many of the reported studies are conducted in homeostasis conditions and, consequently, neglect the impact of the pathologic conditions on the tissue response. To expand our knowledge on the effects of PtNPs on neuronal and glial cells, we investigated the acute effects of monodisperse sodium citrate-coated PtNPs on rat organotypic hippocampal cultures in physiological or neuronal excitotoxic conditions induced by kainic acid (KA). The cellular responses of the PtNPs were evaluated through cytotoxic assays and confocal microscopy analysis. To mimic a pathologic scenario, 7-day organotypic hippocampal cultures were exposed to KA for 24 h. Subsequently, PtNPs were added to each slice. We show that incubation of the slices with PtNPs for 24 h, does not severely impact cell viability in normal conditions, with no significant differences when comparing the dentate gyrus (DG), as well as CA3 and CA1 pyramidal cell layers. Such effects are not exacerbated in KA-treated slices, where the presence of PtNPs does not cause additional neuronal propidium iodide (PI) uptake in CA3 and CA1 pyramidal cell layers. However, PtNPs cause microglial cell activation and morphological alterations in CA3 and DG regions indicating the establishment of an inflammatory reaction. Morphological analysis revealed that microglia acquire activated ameboid morphology with loss of ramifications, as a result of their response to PtNPs contact. Surprisingly, this effect is not increased in pathological conditions. Taken together, these results show that PtNPs cause microglia alterations in short-term studies. Additionally, there is no worsening of the tissue response in a neuropathological induced scenario. This work highlights the need of further research to allow for the safe use of PtNPs. Also, it supports the demand of the development of novel and more biocompatible NPs to be applied in the brain.
Highlights
For many decades, platinum has been employed in many branches of nanobiomedicine (Jeyaraj et al, 2019).This metal presents prodigious physico-chemical characteristics such as good electrical conductivity, chemical stability and surface functionalization, that makes it unique among all the noble metals and suitable for several biomedical applications (Fahmy et al, 2020).Platinum nanoparticles (PtNPs) have recently gained growing interest over Pt derived compounds for the treatment of several types of cancers, thanks to their ability to induce apoptosis and cell cycle arrest, genotoxicity, oxidative stress and morphological changes in the structure of the tumor tissue
These cultures were incubated with monodisperse citrate-coated PtNPs under normal and pathological excitotoxic conditions induced by kainic acid (KA) treatment (Routbort et al, 1999)
To determine the response of the organotypic hippocampal slice cultures to excitotoxic damage induced by KA, we first quantified the uptake of propidium iodide (PI) to assess cell viability after the treatment
Summary
Platinum has been employed in many branches of nanobiomedicine (Jeyaraj et al, 2019).This metal presents prodigious physico-chemical characteristics such as good electrical conductivity, chemical stability and surface functionalization, that makes it unique among all the noble metals and suitable for several biomedical applications (Fahmy et al, 2020).Platinum nanoparticles (PtNPs) have recently gained growing interest over Pt derived compounds for the treatment of several types of cancers, thanks to their ability to induce apoptosis and cell cycle arrest, genotoxicity, oxidative stress and morphological changes in the structure of the tumor tissue. We selected organotypic hippocampal cultures as a model to investigate the biocompatibility of PtNPs and assess the acute response of the brain tissue in terms of cytotoxicity and cellular response These cultures were incubated with monodisperse citrate-coated PtNPs under normal and pathological excitotoxic conditions induced by kainic acid (KA) treatment (Routbort et al, 1999). These stabilized PtNPs were assessed for the cellular responses occurring after short-time contact with brain tissue through cytotoxic and microscopy analysis, focusing on the morphological alterations of neurons, microglia, and astrocytes
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