Polymethine Dye-Functionalized Nanoparticles for Targeting CML Stem Cells.

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.