Immobilization of neurotrophin peptides on gold nanoparticles by direct and lipidmediated interaction: A new multipotential therapeutic nanoplatform for CNS disorders

Neurotrophins are essential proteins for the development and maintenance of neural functions as well as promising drugs in neurodegenerative disorders. Current limits in their effective clinical applications can be overwhelmed by the combined use of peptidomimetic and nanomedicine approaches. Indeed, neurotrophinmimicking peptides may allow minimizing the adverse side effects of the whole protein drug. Moreover, the immobilization of such peptides on nanomaterials may offer additional advantages, including protection against degradation, enhanced permeability of barrier membranes, and intrinsic therapeutic properties of the nanoparticles (e.g., antiangiogenic and plasmonic features of gold nanoparticles (AuNPs)). In the present article, we scrutinize the functionalization of spherical AuNPs of diameter 12 nm by peptides because of the NTerminal domains of the nerve growth factor (NGF) and the brainderived neurotrophic factor (BDNF), NGF114 and BDNF112, respectively. The hybrid goldpeptide nanobiointerface was investigated, both in the direct physisorption and in the lipidbilayermediated adsorption processes, by a multitechnique study that included UVvis and Xray photoelectron spectroscopies, dynamic light scattering, zetapotential analyses, and atomic force microscopy. Both peptideAnd lipiddependent features were identified, to have a modulation in the peptide coverage of nanoparticles as well as in the cellular uptake of NGF and BDNF peptides, as investigated by confocal microscopy. The promising potentials of the neurotrophins to cross the bloodbrain barrier were demonstrated.