Abstract 178: Peptide nanofibers: targeted therapies for glioblastoma multiforme

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.178-178
• Main Authors: Leite, Diana M., Zhu, Rong, Barbu, Eugen, Hinterdorfer, Peter, Pilkington, Geoffrey J., Lalatsa, Aikaterini
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-178

Glioblastoma multiforme (GBM) is a malignant brain tumor with poor prognosis due to tumor heterogeneity, poor drug blood-brain barrier (BBB) permeability and targeting. GBM biopsies indicated the overexpression of G-protein coupled receptors (GPCRs) that when activated by neuropeptide agonists result in an antiproliferative effect. However, translation of these neuropeptides into novel therapies for GBM is frustrated by their short half-life (1.8 mg) ensuring that the resulting nanomedicine can be clinically translatable. Both unloaded- and paclitaxel loaded-nanofibers showed superior stability compared to the parent neuropeptide in the presence of plasma, brain, liver and cell homogenates (>6-fold). Nanofibers elicited a strong antiproliferative effect (IC50: 5.06 μM) resulting in a cell cycle arrest at G2/M in a GPCR positive GBM cell line (U-87 MG). Loading paclitaxel (1nM) within the nanofibers resulted in a synergistic effect evidenced by a decrease in cell survival by 32%. Nanofibers counteracted the forskolin-induced increase of intracellular cAMP levels indicating that the GPCR is linked to the GαI protein known to mediate the antiproliferative effect on GBM. Confocal studies confirmed the internalization of the peptide while SMFS studies supported specific binding of the nanofiber