Interactions of Graphene Oxide and Few-Layer Graphene with the Blood–Brain Barrier

Abstract

Thanks to their biocompatibility and high cargo capability, graphene-based materials (GRMs) might represent an ideal brain delivery system. The capability of GRMs to reach the brain has mainly been investigated in vivo and has highlighted some controversy. Herein, we employed two in vitro BBB models of increasing complexity to investigate the bionano interactions with graphene oxide (GO) and few-layer graphene (FLG): a 2D murine Transwell model, followed by a 3D human multicellular assembloid, to mimic the complexity of the in vivo architecture and intercellular crosstalk. We developed specific methodologies to assess the translocation of GO and FLG in a label-free fashion and a platform applicable to any nanomaterial. Overall, our results show good biocompatibility of the two GRMs, which did not impact the integrity and functionality of the barrier. Sufficiently dispersed subpopulations of GO and FLG were actively uptaken by endothelial cells; however, the translocation was identified as a rare event.

Delivery of graphene oxide nanosheets modulates glutamate release and normalizes amygdala synaptic plasticity to improve anxiety-related behavior

“…55 Our results, in addition to the potential exploitation of the specific s-GO nanosheets as a delivery platform, 56,57 indicate in glutamate vesicle recycling a downstream molecular mechanism underpinning amygdala plasticity which can be the target of future nanotechnology-based treatments. The potential of such approaches is also corroborated by the GO safety in the interaction with the blood-brain barrier, 58 supporting the feasibility of other less invasive routes of administration, alternative to the intrathecal one used in this work. Our PTSD model, using a stressor cue in a classical contextual fear conditioning paradigm, focuses on synaptic changes in the amygdala assuming their implication in PTSD 59 with the potential of the design of novel treatments.…”

Few-layered graphene increases the response of nociceptive neurons to irritant stimuli

“…The presence of large agglomerates of FLG is in line with the low dispersibility of FLG in aqueous-based media. 44 We also observed the FLG flakes' morphology after being processed by the cells for extended periods. We incubated DRG neurons with 10 µg mL −1 of FLG for 24 h (representing the condition for maximum uptake).…”

“…The presence of large agglomerates of FLG is in line with the low dispersibility of FLG in aqueous-based media. 44…”

“…9,30,31,[41][42][43] Instead, low concentrations of small colloidal few-layered graphene (FLG) flakes showed great biocompatibility towards hippocampal neurons, astrocytes, and blood-brain barrier (BBB). 30,31,44 Toxicity studies of GRMs on neurons have mainly focused on the CNS. 9,30,31,45,46 Most of the information about GRMs effects on the peripheral nervous system (PNS) refers to planar graphene-based substrates, intended as scaffolds for nerve regeneration.…”

“…9,30,31,41–43 Instead, low concentrations of small colloidal few-layered graphene (FLG) flakes showed great biocompatibility towards hippocampal neurons, astrocytes, and blood–brain barrier (BBB). 30,31,44…”