EXTH-48. BMP4 BINDING PEPTIDE AMPHIPHILE NANOFIBERS FOR THE TREATMENT OF PEDIATRIC HIGH-GRADE GLIOMAS. (9th November 2020) - Smith, Cara
Abstract: Pediatric high-grade glioma (pHGG) is among the most formidable cancers occurring in childhood. Bone morphogenetic protein 4 (BMP4) reduces the number of glioma stem-like cells and induces apoptosis. Treating tumors with exogenous BMP4 could prove effective in treating gliomas. However, a short half-life limits its clinical application. Glycosylated peptide amphiphile (GlycoPA), with a design inspired by heparin's natural ability to bind growth factors including BMP4 through non-covalent interactions, was previously characterized and found to form high-aspect ratio supramolecular nanofibers that present growth-factor binding sulfated monosaccharides on their surface. These supramolecular nanofibers could carry excessive amounts of growth factor and markedly enhance their biological function. In this study, we verified that GlycoPA is able to bind BMP4 and dramatically increase its half-life with an ELISA assay. We also show that GlycoPA-BMP4, in comparison to free BMP4, significantly decreases pHGG cells' proliferation in vitro . Initial in vivo intracranial distribution experimental results showed that GlycoPA has a superior normal brain distribution in comparison to a control PA (E2 PA) that has the same base structure as GlycoPA except with no glycosylated group. Preliminary results show that GlycoPA-BMP4 markedly decreases pediatric glioma tumor growth in comparison to free BMP4. Our combined in vitro and in vivo results demonstrate PA supramolecular nanofibers as an innovative and promising BMP4 delivery platform for clinical application in the treatment of brain tumors. Our future directions will investigate the therapeutic efficacy of GlycoPA-BMP4 in pediatric HGG through testing large numbers of animals and introducing first-line clinical chemotherapy drugs in combination and in various consequence.