Bibliographic Details
| Title: |
Selective sodium iodide symporter (NIS) gene therapy of glioblastoma mediated by EGFR-targeted lipopolyplexes |
| Authors: |
Rebekka Spellerberg, Teoman Benli-Hoppe, Carolin Kitzberger, Simone Berger, Kathrin A. Schmohl, Nathalie Schwenk, Hsi-Yu Yen, Christian Zach, Franz Schilling, Wolfgang A. Weber, Roland E. Kälin, Rainer Glass, Peter J. Nelson, Ernst Wagner, Christine Spitzweg |
| Source: |
Molecular Therapy: Oncolytics, Vol 23, Iss , Pp 432-446 (2021) |
| Publisher Information: |
Elsevier, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
sodium iodide symporter, NIS, glioblastoma, GBM, gene therapy, polyplexes, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
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. 124I PET imaging allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression, and application of 131I enables cytoreduction. In our experimental design, we used epidermal growth factor receptor (EGFR)-targeted polyplexes (GE11) initially characterized in vitro using 125I uptake assays. Mice bearing an orthotopic glioblastoma were treated subsequently with mono-dibenzocyclooctyne (DBCO)-PEG24-GE11/NIS or bisDBCO-PEG24-GE11/NIS, and 24–48 h later, 124I uptake was assessed by positron emission tomography (PET) imaging. The best-performing polyplex in the imaging studies was then selected for 131I therapy studies. The in vitro studies showed EGFR-dependent and NIS-specific transfection efficiency of the polyplexes. The injection of monoDBCO-PEG24-GE11/NIS polyplexes 48 h before 124I application was characterized to be the optimal regime in the imaging studies and was therefore used for an 131I 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2372-7705 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2372770521001480; https://doaj.org/toc/2372-7705 |
| DOI: |
10.1016/j.omto.2021.10.011 |
| Access URL: |
https://doaj.org/article/a21a2ee7289e45db862f0ab82f5abc16 |
| Accession Number: |
edsdoj.21a2ee7289e45db862f0ab82f5abc16 |
| Database: |
Directory of Open Access Journals |
