Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery

Abstract

Neuroregeneration is the regrowth or repair of nervous tissues, cells, or cell products involved in neurodegeneration and inflammatory diseases of the nervous system like Alzheimer’s disease and Parkinson’s disease. Nowadays, application of nanotechnology is commonly used in developing nanomedicines to advance pharmacokinetics and drug delivery exclusively for central nervous system pathologies. In addition, nanomedical advances are leading to therapies that disrupt disarranged protein aggregation in the central nervous system, deliver functional neuroprotective growth factors, and change the oxidative stress and excitotoxicity of affected neural tissues to regenerate the damaged neurons. Carbon nanotubes and graphene are allotropes of carbon that have been exploited by researchers because of their excellent physical properties and their ability to interface with neurons and neuronal circuits. This review describes the role of carbon nanotubes and graphene in neuroregeneration. In the future, it is hoped that the benefits of nanotechnologies will outweigh their risks, and that the next decade will present huge scope for developing and delivering technologies in the field of neuroscience.

Interfacing Graphene-Based Materials With Neural Cells

“…However, primary neuronal cultures exposed to GO nanosheets displayed clear alterations in a number of physiological pathways, such as calcium and lipid homeostasis, synaptic connectivity and plasticity (Bramini et al, 2016 ; Rauti et al, 2016 ). Once internalized in cells, G nanosheets were seen to preferentially accumulate in lysosomes, as well as to physically damage mitochondria, endoplasmic reticulum and, in some cases, nuclei (John et al, 2015 ). Another study suggested that the irregular protrusions and sharp edges of the nanosheets could damage the plasma membrane, thus letting G entering the cell by piercing the phospholipid-bilayer (Li Y. et al, 2013 ).…”

“…Traditional treatments for central nervous system (CNS) disorders present a number of challenges, thus, developing new tools that outperform the state of the art technologies for imaging, drug delivery, neuronal regeneration and electrical recording and sensing is one of the main goal of modern medicine and neuroscience (Baldrighi et al, 2016 ). Since the development of carbon-related materials, nanotechnology has strongly impacted a number of applications (Figure 1 ) including: drug, gene and protein delivery, to cross the blood-brain barrier (BBB) and reach compromised brain areas; neuro-regenerative techniques to restore cell-cell communication upon damage by interfacing two (2D) or three (3D) dimensional scaffolds with neural cells; highly specific and reliable diagnostic tools, for in vivo sensing of disease biomarkers by cell labeling and real-time monitoring of biological active molecules; and neuronal activity monitoring and modulation, by highly sensitive electrodes for recordings and G-based platforms for electrical local stimulation (Mattei and Rehman, 2014 ; John et al, 2015 ; Chen et al, 2017 ; Kostarelos et al, 2017 ; Reina et al, 2017 ).…”

In Vitro Evaluation of Biocompatibility of Uncoated Thermally Reduced Graphene and Carbon Nanotube-Loaded PVDF Membranes with Adult Neural Stem Cell-Derived Neurons and Glia

“…Graphene, graphene-based nanomaterials (GBNs), and carbon nanotubes (CNTs) are being investigated for their potential applications in tissue engineering and regenerative medicine (Novoselov et al, 2004; John et al, 2015; Marchesan et al, 2015, 2016; Defterali et al, 2016; Lopez-Dolado et al, 2016; Zhou et al, 2016). In fact, scaffolds that support neural growth can be made of porous foams and membranes alone or loaded with a variety of GBNs and CNTs (Ramanathan et al, 2008; Chao et al, 2010; Alvarez et al, 2013; Li et al, 2013; Shah et al, 2014; Song et al, 2014; Weaver and Cui, 2015; Akhavan et al, 2016; Guo et al, 2016b,c).…”

“…CNTs, particularly if used as produced materials, can also induce toxic effects on neural cells in part due to the presence of CNT aggregates, impurities such as amorphous carbon and metallic nanoparticles (Jakubek et al, 2009; Cellot et al, 2010; Wu et al, 2012; Chen et al, 2013; Meng et al, 2013; Bussy et al, 2015). However, recent studies indicate that chemical functionalization can reduce toxicity while preserving the highly conductive character of CNTs (John et al, 2015; Oliveira et al, 2015; Marchesan et al, 2016). …”

Graphene-Derived Materials Interfacing the Spinal Cord: Outstanding in Vitro and in Vivo Findings

“…Major findings discussed in this mini-review article are summarized in Table 1 . Readers are referred to excellent reviews in the topic for further details (Fattahi et al, 2014 ; Fraczek-Szczypta, 2014 ; Nakanishi et al, 2014 ; John et al, 2015 ).…”