Abstract 299: Self-assembling peptide hydrogel for delivery and conversion of temozolomide in glioblastoma treatment

Abstract

Traditional treatment methods for glioblastoma multiforme (GBM) including resection, radiation, and chemotherapy have been largely unsuccessful, with a current 5-year survival rate of 5.6%. In this project we examine the potential of nanosized self-assembling peptide hydrogels to locally deliver and convert temozolomide (TMZ), an FDA-approved pH-sensitive prodrug, for GBM treatment. The peptide hydrogel is designed to load TMZ into the hydrophobic regions of the hydrogels, and during hydrogel degradation in vivo, convert TMZ into its active form. Hydrogel characterization, drug loading and conversion, and cellular uptake and viability are examined to determine the in vitro efficacy of this delivery method. A combination of dynamic light scattering (DLS), scanning electron microscopy (SEM), and circular dichroism (CD) are used to characterize size and structure of the hydrogels. Loading and conversion of TMZ are quantified using UV-Vis spectroscopy. Fluorescent imaging and cell viability assays are used to determine uptake and anti-cancer effects of the drug-loaded hydrogels on glioblastoma cells. Our results show high uptake in drug-resistant T98G and non-resistant LN-18 glioblastoma cell lines using several of our tunable peptide formulations. CD has shown that all peptide formulations form mostly beta-sheet and random structures during self-assembly. SEM and DLS show that peptide hydrogels formed in a water solvent are more polydisperse than hydrogels in a PBS solvent. Using a pH-meter, we have shown that as the peptides in PBS degrade, there is an increase in local pH. Additionally, TMZ conversion is observed to occur more quickly in drug-loaded hydrogels than TMZ alone. Preliminary cell viability studies have shown that unassembled peptides are not cytotoxic; some of the assembled peptide hydrogels are cytotoxic while others maintain greater than 80% viability when compared to untreated cells. Future studies for the project will include cell viability assays with the most promising peptide formulations loaded with TMZ to determine efficacy of the delivery and conversion system. Finally, this project will culminate in an in vivo study to confirm the overall anti-cancer effect of the drug-loaded peptide hydrogels in a tumor model of GBM. Acknowledgements: This research was supported in part by the National Science Foundation EPSCoR Program under NSF Award # OIA-1655740, the National Institute of Health Award # P30GM131959, and National Science Foundation9s Graduate Research Fellowship Program. Citation Format: Megan Pitz, Alexandra Nukovic, Margaret Elpers, Sarah Wilde, Angela Alexander-Bryant. Self-assembling peptide hydrogel for delivery and conversion of temozolomide in glioblastoma treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 299.