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

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 t...

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Main Authors: Wariya Nirachonkul, Siriporn Ogonoki, Tarika Thumvijit, Supanimit Chiampanichayakul, Pawaret Panyajai, Songyot Anuchapreeda, Singkome Tima, Sawitree Chiampanichayakul
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/11/11/2974
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author Wariya Nirachonkul
Siriporn Ogonoki
Tarika Thumvijit
Supanimit Chiampanichayakul
Pawaret Panyajai
Songyot Anuchapreeda
Singkome Tima
Sawitree Chiampanichayakul
author_facet Wariya Nirachonkul
Siriporn Ogonoki
Tarika Thumvijit
Supanimit Chiampanichayakul
Pawaret Panyajai
Songyot Anuchapreeda
Singkome Tima
Sawitree Chiampanichayakul
author_sort Wariya Nirachonkul
collection DOAJ
description 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 IC<sub>50</sub> 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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spelling doaj.art-1060137960654519a4dd0b09051af9732023-11-23T00:41:19ZengMDPI AGNanomaterials2079-49912021-11-011111297410.3390/nano11112974CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem CellsWariya Nirachonkul0Siriporn Ogonoki1Tarika Thumvijit2Supanimit Chiampanichayakul3Pawaret Panyajai4Songyot Anuchapreeda5Singkome Tima6Sawitree Chiampanichayakul7Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandAcute 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 IC<sub>50</sub> 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.https://www.mdpi.com/2079-4991/11/11/2974anti-CD123leukemic stem cellscurcuminacute myeloblastic leukemiananoparticles
spellingShingle Wariya Nirachonkul
Siriporn Ogonoki
Tarika Thumvijit
Supanimit Chiampanichayakul
Pawaret Panyajai
Songyot Anuchapreeda
Singkome Tima
Sawitree Chiampanichayakul
CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells
Nanomaterials
anti-CD123
leukemic stem cells
curcumin
acute myeloblastic leukemia
nanoparticles
title CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells
title_full CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells
title_fullStr CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells
title_full_unstemmed CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells
title_short CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells
title_sort cd123 targeted nano curcumin molecule enhances cytotoxic efficacy in leukemic stem cells
topic anti-CD123
leukemic stem cells
curcumin
acute myeloblastic leukemia
nanoparticles
url https://www.mdpi.com/2079-4991/11/11/2974
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