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Targeted siRNA nanocarrier: a platform technology for cancer treatment
The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescenc...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993695/ https://www.ncbi.nlm.nih.gov/pubmed/35220407 http://dx.doi.org/10.1038/s41388-022-02241-w |
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author | Bäumer, Nicole Tiemann, Jessica Scheller, Annika Meyer, Theresa Wittmann, Lisa Suburu, Matias Ezequiel Gutierrez Greune, Lilo Peipp, Matthias Kellmann, Neele Gumnior, Annika Brand, Caroline Hartmann, Wolfgang Rossig, Claudia Müller-Tidow, Carsten Neri, Dario Strassert, Cristian A. Rüter, Christian Dersch, Petra Lenz, Georg Koeffler, H. Phillip Berdel, Wolfgang E. Bäumer, Sebastian |
author_facet | Bäumer, Nicole Tiemann, Jessica Scheller, Annika Meyer, Theresa Wittmann, Lisa Suburu, Matias Ezequiel Gutierrez Greune, Lilo Peipp, Matthias Kellmann, Neele Gumnior, Annika Brand, Caroline Hartmann, Wolfgang Rossig, Claudia Müller-Tidow, Carsten Neri, Dario Strassert, Cristian A. Rüter, Christian Dersch, Petra Lenz, Georg Koeffler, H. Phillip Berdel, Wolfgang E. Bäumer, Sebastian |
author_sort | Bäumer, Nicole |
collection | PubMed |
description | The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescence microscopy and DLS measurements of these nanocarriers revealed the formation of a vesicular architecture that requires presence of antibody-protamine, defined excess of free SMCC-protamine, and anionic siRNA to form. Only these complex nanoparticles were efficient in the treatment of non-small-cell lung cancer (NSCLC) xenograft models, when the oncogene KRAS was targeted via EGFR-mediated delivery. To show general applicability, we used the modular platform for IGF1R-positive Ewing sarcomas. Anti-IGR1R-antibodies were integrated into an antibody-protamine nanoparticle with an siRNA specifically against the oncogenic translocation product EWS/FLI1. Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi. |
format | Online Article Text |
id | pubmed-8993695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89936952022-04-22 Targeted siRNA nanocarrier: a platform technology for cancer treatment Bäumer, Nicole Tiemann, Jessica Scheller, Annika Meyer, Theresa Wittmann, Lisa Suburu, Matias Ezequiel Gutierrez Greune, Lilo Peipp, Matthias Kellmann, Neele Gumnior, Annika Brand, Caroline Hartmann, Wolfgang Rossig, Claudia Müller-Tidow, Carsten Neri, Dario Strassert, Cristian A. Rüter, Christian Dersch, Petra Lenz, Georg Koeffler, H. Phillip Berdel, Wolfgang E. Bäumer, Sebastian Oncogene Article The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescence microscopy and DLS measurements of these nanocarriers revealed the formation of a vesicular architecture that requires presence of antibody-protamine, defined excess of free SMCC-protamine, and anionic siRNA to form. Only these complex nanoparticles were efficient in the treatment of non-small-cell lung cancer (NSCLC) xenograft models, when the oncogene KRAS was targeted via EGFR-mediated delivery. To show general applicability, we used the modular platform for IGF1R-positive Ewing sarcomas. Anti-IGR1R-antibodies were integrated into an antibody-protamine nanoparticle with an siRNA specifically against the oncogenic translocation product EWS/FLI1. Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi. Nature Publishing Group UK 2022-02-26 2022 /pmc/articles/PMC8993695/ /pubmed/35220407 http://dx.doi.org/10.1038/s41388-022-02241-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bäumer, Nicole Tiemann, Jessica Scheller, Annika Meyer, Theresa Wittmann, Lisa Suburu, Matias Ezequiel Gutierrez Greune, Lilo Peipp, Matthias Kellmann, Neele Gumnior, Annika Brand, Caroline Hartmann, Wolfgang Rossig, Claudia Müller-Tidow, Carsten Neri, Dario Strassert, Cristian A. Rüter, Christian Dersch, Petra Lenz, Georg Koeffler, H. Phillip Berdel, Wolfgang E. Bäumer, Sebastian Targeted siRNA nanocarrier: a platform technology for cancer treatment |
title | Targeted siRNA nanocarrier: a platform technology for cancer treatment |
title_full | Targeted siRNA nanocarrier: a platform technology for cancer treatment |
title_fullStr | Targeted siRNA nanocarrier: a platform technology for cancer treatment |
title_full_unstemmed | Targeted siRNA nanocarrier: a platform technology for cancer treatment |
title_short | Targeted siRNA nanocarrier: a platform technology for cancer treatment |
title_sort | targeted sirna nanocarrier: a platform technology for cancer treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993695/ https://www.ncbi.nlm.nih.gov/pubmed/35220407 http://dx.doi.org/10.1038/s41388-022-02241-w |
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