Bioinspired Nanoplatforms based on Graphene Oxide and Neurotrophin-mimicking Peptides for tissue regeneration

Graphene-based nanomaterials show excellent optical, mechanical, and biological properties. They can be used as a substrate in the field of tissue engineering due to their conductivity, allowing to study and guide neural growth and differentiation. Recent works on graphene oxide (GO) have shown its promising features in regenerative medicine. In this work, the nano-bio interface between the cell membrane and hybrids made of GO nanosheets functionalized with neurotrophin-mimicking peptides was scrutinized to exploit its potential in theranostics (i.e., therapy + imaging/diagnostics) for targeting neurodegenerative diseases as well as angiogenesis. Indeed, neurotrophins, crucial for the functioning of the nervous system, are also known to regulate vascularization. The hybrid peptide-GO systems were assembled by 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 peptide-GO nanoplatforms at the bio interface with artificial cell membranes was scrutinized both in 3D and in 2D, by utilizing model phospholipids self-assembled as small unilamellar vesicles (SUVs) or planar-supported lipid bilayers (SLBs), respectively. The experimental studies were paralleled by 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.