Identification and validation of the binding ligands corresponding to two human glioblastoma penetrating peptides

Abstract

Gliomas are the most common form of primary intracranial malignancy. High-grade gliomas, also called glioblastoma multiforme, are the most frequently encountered, carrying the worst prognosis (12 months life expectancy after diagnosis). Therapy of this brain tumor has been limited by the lack of effective methods for drug delivery, therefore, it is mandatory to seek for new approaches to develop new gliomas therapy strategies.Peptides and proteins which can be internalized by cells have been the subject of intensive study in recent years, since translocation across the cell membrane is critical for drug delivery and gene therapy. Significantly, the advent of the phage display technique has provided a powerful tool, in which bacteriophages are used, in an in vitro process, to select for peptides or proteins that facilitate cell penetration, probably by triggering receptor-mediated endocytosis. During the Tulio Pereira's PhD project: "Characterization of ENC1 (NRP/B) isoforms and identification of human glioblastoma penetrating peptides" (FAPESP Process 2016/01626-9), two different peptides were selected during internalization assays in human glioblastoma cell lines. This three-month internship project is aimed at the identification of the binding ligands corresponding to each of these two peptides, in collaboration with Dr. Renata Pasqualini, who directs an Institute at the University of New Mexico, Albuquerque, New Mexico, USA, being recognized worldwide for her contributions to Oncology using the phage display technology. (AU)