Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma

• DOI: 10.1016/j.omto.2022.10.013
• Publication Date: 2022-11-03T08:10:12Z
• Authors: Rebekka Spellerberg; Teoman Benli-Hoppe; Carolin Kitzberger; Mara Hageneier; Nathalie Schwenk; Özgür Öztürk; Katja Steiger; Gabriele Multhoff; Matthias Eiber; Franz Schilling; Wolfgang A. Weber; Roland E. Kälin; Rainer Glass; Peter J. Nelson; Ernst Wagner; Christine Spitzweg
• Keywords: Sodium-iodide symporter; Transferrin receptor; Targeted Therapy

Sodium iodide symporter (NIS) gene transfer for active accumulation of in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery nucleic acid nanoparticles. present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands transferrin receptor (TfR) epidermal growth factor (EGFR), thus providing potential transport across BBB followed by cells. vitro125I transfection studies confirmed TfR- EGFR-dependent efficiency NIS-specific uptake polyplexes. vivo mice bearing orthotopic U87 GBM xenografts was assessed at 48 h after intravenous polyplex injection positron emission tomography (PET) imaging using 18F-labeled tetrafluoroborate (TFB) as tracer. The tumoral 18F-TFB treated with polyplexes (0.56% ± 0.08% ID/mL) significantly higher compared EGFR-mono-targeted (0.33% 0.03% or TfR-mono-targeted (0.27% 0.04% therapy studies, 131I induced superior effect therapy, demonstrated significant delay prolonged survival.