Effects of silica nanoparticle exposure on mitochondrial function during neuronal differentiation

Abstract

BackgroundNanomedicine offers a promising tool for therapies of brain diseases, but potential effects on neuronal health and neuronal differentiation need to be investigated to assess potential risks. The aim of this study was to investigate effects of silica-indocyanine green/poly (ε-caprolactone) nanoparticles (PCL-NPs) engineered for laser tissue soldering in the brain before and during differentiation of SH-SY5Y cells. Considering adaptations in mitochondrial homeostasis during neuronal differentiation, metabolic effects of PCL-NP exposure before and during neuronal differentiation were studied. In addition, kinases of the PI3 kinase (PI3-K/Akt) and the MAP kinase (MAP-K/ERK) pathways related to neuronal differentiation and mitochondrial function were investigated.ResultsDifferentiation resulted in a decrease in the cellular respiration rate and the extracellular acidification rate (ECAR). PCL-NP exposure impaired mitochondrial function depending on the time of exposure. The cellular respiration rate was significantly reduced compared to differentiated controls when PCL-NPs were given before differentiation. The shift in ECAR was less pronounced in PCL-NP exposure during differentiation. Differentiation and PCL-NP exposure had no effect on expression levels and the enzymatic activity of respiratory chain complexes. The activity of the glycolytic enzyme phosphofructokinase was significantly reduced after differentiation with the effect being more pronounced after PCL-NP exposure before differentiation. The increase in mitochondrial membrane potential observed after differentiation was not found in SH-SY5Y cells exposed to PCL-NPs before differentiation. The cellular adenosine triphosphate (ATP) production significantly dropped during differentiation, and this effect was independent of the PCL-NP exposure. Differentiation and nanoparticle exposure had no effect on superoxide levels at the endpoint of the experiments. A slight decrease in the expression of the neuronal differentiation markers was found after PCL-NP exposure, but no morphological variation was observed.ConclusionsPCL-NP exposure affects mitochondrial function depending on the time of exposure before and during neuronal differentiation. PCL-NP exposure during differentiation was associated with impaired mitochondrial function, which may affect differentiation. Considering the importance of adaptations in cellular respiration for neuronal differentiation and function, further studies are needed to unravel the underlying mechanisms and consequences to assess the possible risks including neurodegeneration.

Leveraging Engineering of Indocyanine Green-Encapsulated Polymeric Nanocomposites for Biomedical Applications

“…In addition, the fluorescence signal avoided the intrinsic background interference relatively, achieving the precision, accuracy, and selectivity of the detection [ 123 , 124 ]. Similarly, Ducray et al prepared ICG-encapsulated silica-PCL nanocomposites for laser tissue soldering, in which the exposure of ICG-encapsulated nanoparticles had significantly affected the mitochondrial function [ 125 ]. In another study, Park et al fabricated ICG sheath incorporated PCL fibers, which exhibited excellent NIR absorption efficiency, acceleration of the ICG release, and the substantial enhancement of the anticancer activity in conjunction with the hyperthermia effect [ 126 ].…”

Impact of nanoparticles on neuron biology: current research trends

“…11 In another study, it was reported that silica-indocyanine green/poly (ε-caprolactone) nanoparticles caused no neuronal differentiation because of mitochondrial damage. 95 We have summarized other nanoparticles that are having inhibitory and cytotoxic effects on neurons, in tabular forms. For example, inhibitory and cytotoxic effects on neurons studied in in vitro models are shown in Table 2, whereas inhibitory and cytotoxic effects studied in animal models are shown in Table 3.…”

Amination of Graphene Oxide Leads to Increased Cytotoxicity in Hepatocellular Carcinoma Cells

“…[54]. Damage of mitochondrial functions can be provoked directly, i.e., by physical interaction of the nanomaterials with the mitochondrial membrane, or indirectly, e.g., by inducing damages through interactions with cell membrane protein receptors [56][57][58][59]. It is known that DNA is a critical target of ROS.…”

“…Maximal acidification was calculated as the mean of three ECAR measurement cycles after oligomycin injection. The OCR data were corrected for non-mitochondrial oxygen consumption under rotenone and antimycin A [59]. Two repetitions of the Seahorse experiments were performed for data quantitation.…”