Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma

Int J Pharm X. 2022 Sep 22:4:100128. doi: 10.1016/j.ijpx.2022.100128. eCollection 2022 Dec.

Abstract

NFL-TBS.40-63 peptide is a recently discovered peptide derived from the light neurofilament chain (NFL). In this study, we demonstrated that the Biotinylated-NFL-peptide (BIOT-NFL) can spontaneously self-assemble into well-organized nanofibers (approximately 5 nm width and several micrometers in length) in several solutions, whereas the typical self-assembly was not systematically observed from other peptides with or without coupling. The critical aggregation concentration that allows the BIOT-NFL-peptide to aggregate and auto associate was determined at 10-4 mol/L by surface tension measurements. X-ray scattering of BIOT-NFL-peptide also demonstrated its beta-sheet structure that can facilitate the intermolecular interactions involved in the self-assembly process. The possible disassembly of self-assembled BIOT-NFL-peptide-nanofibers was examined via a dialysis membrane study. We further investigated the interaction between nanofibers formed by BIOT-NFL-peptide and gold nanoparticles. Interestingly, a strong interaction was demonstrated between these nanoparticles and BIOT-NFL-peptide resulted in the formation of BIOT-NFL-peptide-nanofibers grandly decorated by gold nanoparticles. Finally, we investigated the internalization of gold nanoparticles coupled with BIOT-NFL-nanofibers into F98 rat glioblastoma cells, which was increased compared to the non-coupled control gold nanoparticles. All these results indicate that this peptide could be a promising therapeutic agent for targeted delivery.

Keywords: BIOT-NFL, the NFL-TBS.40–63 peptide coupled to the biotin; BIOT-NFL-peptide-nanofibers; CAC, critical aggregation concentration; DMEM, dulbecco's modified eagle medium; FAM-NFL, the NFL-TBS.40–63 peptide coupled to 5-carboxy-fluorescein; Glioblastoma; Gold nanoparticles; NFL-SCR, the scrambled NFL-TBS.40–63 peptide (with the same amino acids as the NFL-peptide but in a different order); NFL-TBS.40-63 peptide; NFL-peptide, neurofilament light subunit derived 24 amino acid tubulin-binding site peptide NFL-TBS.40–63; SDS, sodium dodecyl sulfate; Self-assembly; TEM, transmission electron microscopy; Targeted drug delivery; UPLC, ultra-performance liquid chromatography system; XRS, x-ray scattering; aCSF, artificial cerebrospinal fluid; nude-NFL, the NFL-TBS.40–63 peptide with no labeling.