Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells
In chronic myelogenous leukemia (CML), treatment with tyrosine kinase inhibitors (TKI) is unable to eradicate leukemic stem cells (LSC). Polymethine dye-functionalized nanoparticles can be internalized by specific cell types using transmembrane carrier proteins. In this study we investigated the upt...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S237277052030111X |
| _version_ | 1819296486360350720 |
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| author | Philipp Ernst Adrian T. Press Mike Fischer Vivien Günther Christine Gräfe Joachim H. Clement Thomas Ernst Ulrich S. Schubert Jana Wotschadlo Marc Lehmann Christoph Enzensperger Michael Bauer Andreas Hochhaus |
| author_facet | Philipp Ernst Adrian T. Press Mike Fischer Vivien Günther Christine Gräfe Joachim H. Clement Thomas Ernst Ulrich S. Schubert Jana Wotschadlo Marc Lehmann Christoph Enzensperger Michael Bauer Andreas Hochhaus |
| author_sort | Philipp Ernst |
| collection | DOAJ |
| description | In chronic myelogenous leukemia (CML), treatment with tyrosine kinase inhibitors (TKI) is unable to eradicate leukemic stem cells (LSC). Polymethine dye-functionalized nanoparticles can be internalized by specific cell types using transmembrane carrier proteins. In this study we investigated the uptake behavior of various polymethine dyes on leukemia cell lines and searched for carrier proteins that guide dye transport using RNA interference. The results show that the uptake of DY-635 is dependent on organic anion transport protein 1B3 (OATP1B3) in CML cells and immature myeloid precursor cells of CML patients. In contrast to nonspecific poly(lactide-co-glycolic acid) (PLGA) nanoparticle constructs, DY-635-functionalization of nanoparticles led to an uptake in CML cells. Investigation of these nanoparticles on bone marrow of CML patients showed a preferred uptake in LSC. The transcription of OATP1B3 is known to be induced under hypoxic conditions via the hypoxia-inducing factor 1 alpha (HIF1α), thus also in the stem cells niche. Since these cells have the potential to repopulate the bone marrow after CML treatment discontinuation, eliminating them by means of drug-loaded DY-635-functionalized PLGA nanoparticles deployed as a selective delivery system to LSC is highly relevant to the ongoing search for curative treatment options for CML patients. |
| first_indexed | 2024-12-24T04:58:52Z |
| format | Article |
| id | doaj.art-67947521e5e3418a85f1055be7115221 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-24T04:58:52Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-67947521e5e3418a85f1055be71152212022-12-21T17:14:17ZengElsevierMolecular Therapy: Oncolytics2372-77052020-09-0118372381Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem CellsPhilipp Ernst0Adrian T. Press1Mike Fischer2Vivien Günther3Christine Gräfe4Joachim H. Clement5Thomas Ernst6Ulrich S. Schubert7Jana Wotschadlo8Marc Lehmann9Christoph Enzensperger10Michael Bauer11Andreas Hochhaus12Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany; Else-Kröner-Forschungskolleg, Jena, Germany; Corresponding author: Philipp Ernst, Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany.Klinik für Anästhesiologie und Intensivmedizin, Center for Sepsis Control and Care (CSCC), Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyKlinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyKlinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyKlinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyKlinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyKlinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyJena Center for Soft Matter (JCSM), Friedrich Schiller Universität Jena, Philosophenweg 7, 07743 Jena, Germany; Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller Universität Jena, Humboldtstrasse 10, 07743 Jena, GermanySmartDyeLivery GmbH, Botzstrasse 5, 07743 Jena, GermanySmartDyeLivery GmbH, Botzstrasse 5, 07743 Jena, GermanySmartDyeLivery GmbH, Botzstrasse 5, 07743 Jena, GermanyKlinik für Anästhesiologie und Intensivmedizin, Center for Sepsis Control and Care (CSCC), Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich Schiller Universität Jena, Philosophenweg 7, 07743 Jena, GermanyKlinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, GermanyIn chronic myelogenous leukemia (CML), treatment with tyrosine kinase inhibitors (TKI) is unable to eradicate leukemic stem cells (LSC). Polymethine dye-functionalized nanoparticles can be internalized by specific cell types using transmembrane carrier proteins. In this study we investigated the uptake behavior of various polymethine dyes on leukemia cell lines and searched for carrier proteins that guide dye transport using RNA interference. The results show that the uptake of DY-635 is dependent on organic anion transport protein 1B3 (OATP1B3) in CML cells and immature myeloid precursor cells of CML patients. In contrast to nonspecific poly(lactide-co-glycolic acid) (PLGA) nanoparticle constructs, DY-635-functionalization of nanoparticles led to an uptake in CML cells. Investigation of these nanoparticles on bone marrow of CML patients showed a preferred uptake in LSC. The transcription of OATP1B3 is known to be induced under hypoxic conditions via the hypoxia-inducing factor 1 alpha (HIF1α), thus also in the stem cells niche. Since these cells have the potential to repopulate the bone marrow after CML treatment discontinuation, eliminating them by means of drug-loaded DY-635-functionalized PLGA nanoparticles deployed as a selective delivery system to LSC is highly relevant to the ongoing search for curative treatment options for CML patients.http://www.sciencedirect.com/science/article/pii/S237277052030111Xpolymethine dyesnanoparticlesCMLOATP1B3OCT1 |
| spellingShingle | Philipp Ernst Adrian T. Press Mike Fischer Vivien Günther Christine Gräfe Joachim H. Clement Thomas Ernst Ulrich S. Schubert Jana Wotschadlo Marc Lehmann Christoph Enzensperger Michael Bauer Andreas Hochhaus Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells Molecular Therapy: Oncolytics polymethine dyes nanoparticles CML OATP1B3 OCT1 |
| title | Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells |
| title_full | Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells |
| title_fullStr | Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells |
| title_full_unstemmed | Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells |
| title_short | Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells |
| title_sort | polymethine dye functionalized nanoparticles for targeting cml stem cells |
| topic | polymethine dyes nanoparticles CML OATP1B3 OCT1 |
| url | http://www.sciencedirect.com/science/article/pii/S237277052030111X |
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