Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452122/ https://www.ncbi.nlm.nih.gov/pubmed/32913887 http://dx.doi.org/10.1016/j.omto.2020.07.007 |
_version_ | 1783575112938684416 |
---|---|
author | Ernst, Philipp Press, Adrian T. Fischer, Mike Günther, Vivien Gräfe, Christine Clement, Joachim H. Ernst, Thomas Schubert, Ulrich S. Wotschadlo, Jana Lehmann, Marc Enzensperger, Christoph Bauer, Michael Hochhaus, Andreas |
author_facet | Ernst, Philipp Press, Adrian T. Fischer, Mike Günther, Vivien Gräfe, Christine Clement, Joachim H. Ernst, Thomas Schubert, Ulrich S. Wotschadlo, Jana Lehmann, Marc Enzensperger, Christoph Bauer, Michael Hochhaus, Andreas |
author_sort | Ernst, Philipp |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7452122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-74521222020-09-09 Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells Ernst, Philipp Press, Adrian T. Fischer, Mike Günther, Vivien Gräfe, Christine Clement, Joachim H. Ernst, Thomas Schubert, Ulrich S. Wotschadlo, Jana Lehmann, Marc Enzensperger, Christoph Bauer, Michael Hochhaus, Andreas Mol Ther Oncolytics Article 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. American Society of Gene & Cell Therapy 2020-07-25 /pmc/articles/PMC7452122/ /pubmed/32913887 http://dx.doi.org/10.1016/j.omto.2020.07.007 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ernst, Philipp Press, Adrian T. Fischer, Mike Günther, Vivien Gräfe, Christine Clement, Joachim H. Ernst, Thomas Schubert, Ulrich S. Wotschadlo, Jana Lehmann, Marc Enzensperger, Christoph Bauer, Michael Hochhaus, Andreas Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452122/ https://www.ncbi.nlm.nih.gov/pubmed/32913887 http://dx.doi.org/10.1016/j.omto.2020.07.007 |
work_keys_str_mv | AT ernstphilipp polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT pressadriant polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT fischermike polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT gunthervivien polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT grafechristine polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT clementjoachimh polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT ernstthomas polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT schubertulrichs polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT wotschadlojana polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT lehmannmarc polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT enzenspergerchristoph polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT bauermichael polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells AT hochhausandreas polymethinedyefunctionalizednanoparticlesfortargetingcmlstemcells |