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Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells.

Philipp Ernst1,2, Adrian T Press3, Mike Fischer1

  • 1Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany.

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Summary
This summary is machine-generated.

Targeting leukemic stem cells (LSC) in chronic myelogenous leukemia (CML) is crucial. Polymethine dye-functionalized nanoparticles selectively target LSC via OATP1B3, offering a potential curative strategy for CML.

Keywords:
CMLOATP1B3OCT1nanoparticlespolymethine dyes

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Hematology

Background:

  • Chronic myelogenous leukemia (CML) treatment with tyrosine kinase inhibitors (TKI) fails to eradicate leukemic stem cells (LSC).
  • Leukemic stem cells (LSC) are responsible for disease relapse and resistance to current therapies.
  • Targeting LSC is essential for developing curative strategies for CML.

Purpose of the Study:

  • To investigate the uptake of polymethine dyes by leukemia cells.
  • To identify carrier proteins involved in dye transport using RNA interference.
  • To evaluate the potential of functionalized nanoparticles as a targeted delivery system for LSC in CML.

Main Methods:

  • Investigated uptake of various polymethine dyes on leukemia cell lines.
  • Utilized RNA interference to identify carrier proteins for dye transport.
  • Functionalized poly(lactide-co-glycolic acid) (PLGA) nanoparticles with DY-635 dye.
  • Analyzed nanoparticle uptake in bone marrow samples from CML patients.

Main Results:

  • DY-635 uptake was dependent on organic anion transport protein 1B3 (OATP1B3) in CML cells and myeloid precursors.
  • DY-635-functionalized nanoparticles showed preferential uptake in LSC from CML patient bone marrow.
  • OATP1B3 transcription is induced by hypoxia-inducing factor 1 alpha (HIF1α) in the stem cell niche.

Conclusions:

  • DY-635-functionalized PLGA nanoparticles selectively target LSC in CML.
  • The OATP1B3 transporter mediates the uptake of DY-635 in CML and LSC.
  • This targeted delivery system holds promise for eradicating LSC and achieving a cure for CML.