Abstract
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 (NIS). Due to its iodide trapping activity, NIS is a powerful theranostic tool for diagnostic imaging and the application of therapeutic radionuclides. I-124 PET imaging allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression, and application of I-131 enables cytoreduction. In our experimental design, we used epidermal growth factor receptor (EGFR)-targeted polyplexes (GE11) initially characterized in vitro using I-125 uptake assays. Mice bearing an orthotopic glioblastoma were treated subsequently with mono-dibenzocyclooctyne (DBCO)-(PEG24-)GE11/NIS or bisDBCO-PEG(24)-GE11/NIS, and 24-48 h later, I-124 uptake was assessed by positron emission tomography (PET) imaging. The best-performing polyplex in the imaging studies was then selected for I-131 therapy studies. The in vitro studies showed EGFR-dependent and NIS-specific transfection efficiency of the polyplexes. The injection of monoDBCO-PEG(24)-GE11/NIS polyplexes 48 h before I-124 application was characterized to be the optimal regime in the imaging studies and was therefore used for an I-131 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 NIS gene therapy as a new strategy for the therapy of glioblastoma.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 2372-7705 |
Language: | English |
Item ID: | 102241 |
Date Deposited: | 05. Jun 2023, 15:39 |
Last Modified: | 17. Oct 2023, 15:10 |