CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells

Abstract

Acute myeloblastic leukemia (AML) is a disease with a high rate of relapse and drug resistance due to the remaining leukemic stem cells (LSCs). Therefore, LSCs are specific targets for the treatment of leukemia. CD123 is specifically expressed on LSCs and performs as a specific marker. Curcumin is the main active compound of a natural product with low toxicity for humans. It has been reported to inhibit leukemic cell growth. However, curcumin is practically insoluble in water and has low bioavailability. In this study, we aimed to formulate curcumin nanoparticles and conjugate with the anti-CD123 to overcome the low water solubility and improve the targeting of LSCs. The cytotoxicity of both curcumin-loaded PLGA/poloxamer nanoparticles (Cur-NPs) and anti-CD123-curcumin-loaded PLGA/poloxamer nanoparticles (anti-CD123-Cur-NPs) were examined in KG-1a cells. The results showed that Cur-NPs and Cur-NPs-CD123 exhibited cytotoxic effects on KG-1a cells with the IC50 values of 74.20 ± 6.71 and 41.45 ± 5.49 µM, respectively. Moreover, anti-CD123-Cur-NPs induced higher apoptosis than Cur-NPs. The higher uptake of anti-CD123-Cur-NPs in KG-1a cells was confirmed by using flow cytometry. In conclusion, the anti-CD123-Cur-NPs formulation improved curcumin’s bioavailability and specific targeting of LSCs, suggesting that it is a promising drug delivery system for improving the therapeutic efficacy against AML.

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“…The gradual release of artemether, the improvement of stability, and solubility due to the conversion of the free form of artemether to the nanoparticle form are some of the reasons that increase the effect of nanoparticles compared to artemether. A comparison of IC 50 results with similar articles shows that the difference between the IC 50 value of nanoparticles and free artemether is significant [ 45 , 73 ]. According to Figure 6 , the results of the IC50 calculation show that artemether encapsulation with albumin reduces the effective dose of the drug.…”

Potent anti-tumor activity of CD45RA-targeting Hm3A4-Ranpirnase against myeloid lineage leukemias

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Phytochemical-based nanodrugs going beyond the state-of-the-art in cancer management—Targeting cancer stem cells in the framework of predictive, preventive, personalized medicine

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