Bioinspired Nanoplatforms Based on Graphene Oxide and Neurotrophin-Mimicking Peptides

Abstract

Neurotrophins (NTs), which are crucial for the functioning of the nervous system, are also known to regulate vascularization. Graphene-based materials may drive neural growth and differentiation, and, thus, have great potential in regenerative medicine. In this work, we scrutinized the nano–biointerface between the cell membrane and hybrids made of neurotrophin-mimicking peptides and graphene oxide (GO) assemblies (pep−GO), to exploit their potential in theranostics (i.e., therapy and imaging/diagnostics) for targeting neurodegenerative diseases (ND) as well as angiogenesis. The pep−GO systems were assembled via spontaneous physisorption onto GO nanosheets of the peptide sequences BDNF(1-12), NT3(1-13), and NGF(1-14), mimicking the brain-derived neurotrophic factor (BDNF), the neurotrophin 3 (NT3), and the nerve growth factor (NGF), respectively. The interaction of pep−GO nanoplatforms at the biointerface with artificial cell membranes was scrutinized both in 3D and 2D by utilizing model phospholipids self-assembled as small unilamellar vesicles (SUVs) or planar-supported lipid bilayers (SLBs), respectively. The experimental studies were paralleled via molecular dynamics (MD) computational analyses. Proof-of-work in vitro cellular experiments with undifferentiated neuroblastoma (SH-SY5Y), neuron-like, differentiated neuroblastoma (dSH-SY5Y), and human umbilical vein endothelial cells (HUVECs) were carried out to shed light on the capability of the pep−GO nanoplatforms to stimulate the neurite outgrowth as well as tubulogenesis and cell migration.

A multi-channel collagen conduit with aligned Schwann cells and endothelial cells for enhanced neuronal regeneration in spinal cord injury

“…The secreted BDNF repairs nerve tissues by inducing EC survival and angiogenic tube formation, and NTs induce axonal growth by promoting the expression of angiogenic factors, such as VEGF. 72 Angiogenesis is induced by paracrine factors in SCs and ECs, which enhance neuronal regeneration. Additionally, the poor survival of transplanted SCs and ECs limits their therapeutic effect.…”

The Hybrid Nano-Biointerface between Proteins/Peptides and Two-Dimensional Nanomaterials

“…MD investigations have also demonstrated the graphene's capability to elicit toxicity by interfering with protein-protein interactions (PPI). Simulations of PPI in the presence and absence of graphene showed that graphene inserted into PP led to the destabilization of hydrophobic interactions, disrupting the protein complex [99]; see Figure 3 Molecular dynamics simulations were carried out to study the interface between neurotrophin-mimicking peptides [100][101][102] non-covalently linked to the surface of GO [103]. Among the peptides under investigation, NGF (1-14) exhibited the strongest interaction with the GO substrate.…”

“…Notably, the glutamic acid residue assumes a crucial role since this moiety appears highly distanced from the surface in the case of BDNF (1-12), which coincides with the peptide displaying the lowest interaction energy; see Figure 4. Molecular dynamics simulations were carried out to study the interface between neurotrophin-mimicking peptides [100][101][102] non-covalently linked to the surface of GO [103]. Among the peptides under investigation, NGF (1-14) exhibited the strongest interaction with the GO substrate.…”