Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma
Sodium iodide symporter (NIS) gene transfer for active accumulation of iodide in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application of radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery barrier for nu...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770522001358 |
| _version_ | 1811304687900557312 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rebekka Spellerberg |
| collection | DOAJ |
| description | Sodium iodide symporter (NIS) gene transfer for active accumulation of iodide in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application of radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery barrier for nucleic acid nanoparticles. In the present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands for the transferrin receptor (TfR) and the epidermal growth factor receptor (EGFR), thus providing the potential for active transport across the BBB followed by targeting of tumor cells. In vitro 125I transfection studies confirmed TfR- and EGFR-dependent transfection efficiency and NIS-specific iodide uptake of dual-targeted polyplexes. In vivo gene transfer in mice bearing orthotopic U87 GBM xenografts was assessed at 48 h after intravenous polyplex injection by positron emission tomography (PET) imaging using 18F-labeled tetrafluoroborate (TFB) as tracer. The tumoral 18F-TFB uptake of mice treated with dual-targeted polyplexes (0.56% ± 0.08% ID/mL) was significantly higher compared with mice treated with EGFR-mono-targeted (0.33% ± 0.03% ID/mL) or TfR-mono-targeted (0.27% ± 0.04% ID/mL) polyplexes. In therapy studies, application of 131I induced a superior therapeutic effect of the dual-targeted therapy, demonstrated by a significant delay in tumor growth and prolonged survival. |
| first_indexed | 2024-04-13T08:11:48Z |
| format | Article |
| id | doaj.art-a363261d210f4561be309e89accd3fb1 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-04-13T08:11:48Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-a363261d210f4561be309e89accd3fb12022-12-22T02:54:59ZengElsevierMolecular Therapy: Oncolytics2372-77052022-12-0127272287Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastomaRebekka Spellerberg0Teoman Benli-Hoppe1Carolin Kitzberger2Mara Hageneier3Nathalie Schwenk4Özgür Öztürk5Katja Steiger6Gabriele Multhoff7Matthias Eiber8Franz Schilling9Wolfgang A. Weber10Roland E. Kälin11Rainer Glass12Peter J. Nelson13Ernst Wagner14Christine Spitzweg15Department of Internal Medicine IV, LMU University Hospital, LMU Munich, Munich, GermanyPharmaceutical Biotechnology, Department of Pharmacy, Centre for System-Based Drug Research, and Centre for Nanoscience, LMU Munich, Munich, GermanyDepartment of Internal Medicine IV, LMU University Hospital, LMU Munich, Munich, GermanyDepartment of Internal Medicine IV, LMU University Hospital, LMU Munich, Munich, GermanyDepartment of Internal Medicine IV, LMU University Hospital, LMU Munich, Munich, GermanyPharmaceutical Biotechnology, Department of Pharmacy, Centre for System-Based Drug Research, and Centre for Nanoscience, LMU Munich, Munich, GermanyInstitute of Pathology, School of Medicine, Technical University of Munich, Munich, GermanyCenter for Translational Cancer Research, Radiation Immuno-Oncology Group, School of Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, GermanyDepartment of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, GermanyDepartment of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, GermanyDepartment of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, GermanyNeurosurgical Research, Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany; Walter Brendel Center of Experimental Medicine, Faculty of Medicine, LMU Munich, Munich, GermanyNeurosurgical Research, Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany; Walter Brendel Center of Experimental Medicine, Faculty of Medicine, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Internal Medicine IV, LMU University Hospital, LMU Munich, Munich, GermanyPharmaceutical Biotechnology, Department of Pharmacy, Centre for System-Based Drug Research, and Centre for Nanoscience, LMU Munich, Munich, GermanyDepartment of Internal Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA; Corresponding author Christine Spitzweg, University Hospital, LMU Munich, Department of Internal Medicine IV, Marchioninistrasse 15, 81377 Munich, Germany.Sodium iodide symporter (NIS) gene transfer for active accumulation of iodide in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application of radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery barrier for nucleic acid nanoparticles. In the present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands for the transferrin receptor (TfR) and the epidermal growth factor receptor (EGFR), thus providing the potential for active transport across the BBB followed by targeting of tumor cells. In vitro 125I transfection studies confirmed TfR- and EGFR-dependent transfection efficiency and NIS-specific iodide uptake of dual-targeted polyplexes. In vivo gene transfer in mice bearing orthotopic U87 GBM xenografts was assessed at 48 h after intravenous polyplex injection by positron emission tomography (PET) imaging using 18F-labeled tetrafluoroborate (TFB) as tracer. The tumoral 18F-TFB uptake of mice treated with dual-targeted polyplexes (0.56% ± 0.08% ID/mL) was significantly higher compared with mice treated with EGFR-mono-targeted (0.33% ± 0.03% ID/mL) or TfR-mono-targeted (0.27% ± 0.04% ID/mL) polyplexes. In therapy studies, application of 131I induced a superior therapeutic effect of the dual-targeted therapy, demonstrated by a significant delay in tumor growth and prolonged survival.http://www.sciencedirect.com/science/article/pii/S2372770522001358sodium iodide symporterNISradioiodineblood-brain barrierEGFRtransferrin receptor |
| spellingShingle | 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 Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma Molecular Therapy: Oncolytics sodium iodide symporter NIS radioiodine blood-brain barrier EGFR transferrin receptor |
| title | Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma |
| title_full | Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma |
| title_fullStr | Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma |
| title_full_unstemmed | Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma |
| title_short | Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma |
| title_sort | dual egfr and tfr targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma |
| topic | sodium iodide symporter NIS radioiodine blood-brain barrier EGFR transferrin receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2372770522001358 |
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