Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby 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 (NIS). Due to its iodide trapping activity, NIS is a powerful theranostic tool for diagnostic imaging and t...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	sodium iodide symporter NIS glioblastoma GBM gene therapy polyplexes Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a21a2ee7289e45db862f0ab82f5abc16
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spelling	oai:doaj.org-article:a21a2ee7289e45db862f0ab82f5abc162021-11-18T04:50:28ZSelective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes2372-770510.1016/j.omto.2021.10.011https://doaj.org/article/a21a2ee7289e45db862f0ab82f5abc162021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001480https://doaj.org/toc/2372-7705Lipo-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.Rebekka SpellerbergTeoman Benli-HoppeCarolin KitzbergerSimone BergerKathrin A. SchmohlNathalie SchwenkHsi-Yu YenChristian ZachFranz SchillingWolfgang A. WeberRoland E. KälinRainer GlassPeter J. NelsonErnst WagnerChristine SpitzwegElsevierarticlesodium iodide symporterNISglioblastomaGBMgene therapypolyplexesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 432-446 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sodium iodide symporter NIS glioblastoma GBM gene therapy polyplexes Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	sodium iodide symporter NIS glioblastoma GBM gene therapy polyplexes Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes
description	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.
format	article
author	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
author_facet	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
author_sort	Rebekka Spellerberg
title	Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes
title_short	Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes
title_full	Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes
title_fullStr	Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes
title_full_unstemmed	Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes
title_sort	selective sodium iodide symporter (nis) genetherapy of glioblastoma mediatedby egfr-targeted lipopolyplexes
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a21a2ee7289e45db862f0ab82f5abc16
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Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes

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