Selective sodium iodide symporter (NIS) gene therapy of glioblastoma mediated by EGFR-targeted lipopolyplexes

Lipo-oligomers, post-functionalized with ligands to enhance targeting, represent promising new vehicles for the tumor-specific delivery of therapeutic genes such as the sodium iodide symporter (). Due to its iodide trapping activity, NIS is a powerful theranostic tool for diagnostic imaging and the application of therapeutic radionuclides. I PET imaging allows non-invasive monitoring of the biodistribution of functional NIS expression, and application of I enables cytoreduction. In our experimental design, we used epidermal growth factor receptor (EGFR)-targeted polyplexes (GE11) initially characterized using I uptake assays. Mice bearing an orthotopic glioblastoma were treated subsequently with mono-dibenzocyclooctyne (DBCO)-PEG-GE11/NIS or bisDBCO-PEG-GE11/NIS, and 24-48 h later, I uptake was assessed by positron emission tomography (PET) imaging. The best-performing polyplex in the imaging studies was then selected for I therapy studies. The studies showed EGFR-dependent and NIS-specific transfection efficiency of the polyplexes. The injection of monoDBCO-PEG-GE11/NIS polyplexes 48 h before I application was characterized to be the optimal regime in the imaging studies and was therefore used for an I therapy study, showing a significant decrease in tumor growth and a significant extension of survival in the therapy group. These studies demonstrate the potential of EGFR-targeted polyplex-mediated gene therapy as a new strategy for the therapy of glioblastoma.