De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells

Abstract

Glioblastoma multiforme (GBM) is the most aggressive central nervous system tumor, and standard treatment, including surgical resection, radiation, and chemotherapy, has not significantly improved patient outcomes over the last 20 years. Temozolomide (TMZ), the prodrug most commonly used to treat GBM, must pass the blood–brain barrier and requires a basic pH to convert to its active form. Due to these barriers, less than 30% of orally delivered TMZ reaches the central nervous system and becomes bioactive. In this work, we have developed a novel biomaterial delivery system to convert TMZ to its active form and that shows promise for intracellular TMZ delivery. Self-assembling peptides were characterized under several different assembly conditions and evaluated for TMZ loading and conversion. Both solvent and method of assembly were found to affect the supramolecular and secondary structure of peptide assemblies. Additionally, as peptides degraded in phosphate-buffered saline, TMZ was rapidly converted to its active form. This work demonstrates that peptide-based drug delivery systems can effectively create a local stimulus during drug delivery while remaining biocompatible. This principle could be used in many future biomedical applications in addition to cancer treatment, such as wound healing and regenerative medicine.

Electrospun Drug-Loaded and Gene-Loaded Nanofibres: The Holy Grail of Glioblastoma Therapy?

“…Another type of polymer studied is peptide nano assemblies, which have shown remarkable properties in sustaining drug and gene release for delivery into tumour cells. Due to their ability to form a wide range of nanostructures, self-assembling peptide hydrogels are used [ 55 ]. Lebedenko et al [ 56 ] developed new peptide conjugates by amalgamating the anti-inflammatory antitumour compound azelaic acid with angiopep-2, which efficiently self-assembled into nanofibres.…”