Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus

Abstract

Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus.

Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane

“…Others evaluated SWCNT cytotoxicity using THP1 monocytes and showed that SWCNTs were cytotoxic to THP1 cells grown in 2D cell culture conditions but were not cytotoxic to cells grown in the 3D tissue-mimetic model(Movia et al, 2011). PEG functionalized SWCNTs also did not induce significant morphological alterations in rat hippocampus(Dal Bosco et al, 2015). Similarly, we found that DSPE-PEG coated, acid oxidized MWCNTs were cytotoxic to glioblastoma cells grown in two-dimensional monolayer, but had no observable effect on growth of glioblastoma cells grown as three-dimensional spheroids(Eldridge et al, 2016).…”

Interaction of single‐walled carbon nanotubes and saxitoxin: Ab initio simulations and biological responses in hippocampal cell line HT‐22

“…According to a previous study , the fluorescence emission of isolated SWCNTs appears in the 900‐nm to 1400‐nm range, greater than the emission wavelength used in the present study. In addition, no interference from pegylated SWCNTs was observed in H 2 DCF‐DA fluorescence generation . The ROS area was standardized by the number of viable cells, and ROS levels were expressed in terms of fluorescence area, where the area was obtained by integrating the fluorescence units (FU) over the measurement time (90 min) and expressed as FU/min.…”

“…Indeed, in vitro studies have confirmed that exposure to different CNTs causes oxidative damage and increases ROS in a cell type–dependent manner. Moreover, SWCNTs functionalized with polyethylene glycol (SWCNT‐PEG) and directly infused into rat hippocampus reduced ROS and induced antioxidant defenses 7 d after injection, suggesting that the biopersistence of nanomaterial in the tissue can induce an antioxidant response .…”

Redox‐Responsive Nanobiomaterials‐Based Therapeutics for Neurodegenerative Diseases

“…PEGylated SWCNTs exhibited increased biopersistence in the tissue and could initiate a delayed antioxidant defense after administration into the rat hippocampus. [179]…”