Nanoparticles design for neuron targeting

Abstract

ABSTRACT : Neurodegenerative diseases are a group of progressive and degenerative disorders that affects the nervous system and causes various symptoms in patients with these pathologies. Unfortunately, there is no cure for these diseases, so treatment aims to alleviate symptoms, prevent complications, and slow the progression. In this research, we propose a carrier nanosystem that uses spherical silica nanoparticles functionalized with the toxin ligand domain derived from Clostridium botulinum toxin (BTXC), which binds with high affinity with the SV2 motoneuron´s receptor, so this nanosystem could reach the nervous system through retro-axonal transport Silica nanoparticles were synthesized through the Stöber method, obtaining negative charge particles that will bind electrostatically with the histidine tails (positive charge) of the toxin ligand domain. BTXC was overexpressed, extracted, and purified from E. coli. Nanoparticles loaded with FITC were functionalized and added to motoneurons like cell cultures (NSC34) to determine if the toxin ligand domain gives the nanoparticles specificity for neurons. Flow cytometry demonstrated that the BTXC ligand increased the affinity of nanoparticles for motoneurons-like cells. In addition, to evaluate the gene delivery ability of this nanosystem, nanoparticles that contain the DNA were synthesized, then functionalized with BTXC and added to NSC34 cells, the gene expression was evaluated by fluorescence microscopy and flow cytometry. These results indicate that BTXC functionalization gives these carrier nanosystems affinity for motoneurons-like cell cultures. Furthermore, they have shown the ability to encapsulate biological material inside, which would be an important gene therapy for future neurodegenerative disease treatment.