Cytotoxicity of Doxorubicin-Curcumin Nanoparticles Conjugated with Two Different Peptides (CKR and EVQ) against FLT3 Protein in Leukemic Stem Cells.

Autor: Chueahongthong F; Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.; Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand., Chiampanichayakul S; Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.; Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand.; Cancer Research Unit of Associated Medical Sciences (AMS-CRU), Chiang Mai University, Chiang Mai 50200, Thailand., Viriyaadhammaa N; Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.; Cancer Research Unit of Associated Medical Sciences (AMS-CRU), Chiang Mai University, Chiang Mai 50200, Thailand., Dejkriengkraikul P; Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand., Okonogi S; Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand.; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand., Berkland C; Department of Biomedical Engineering and Department of Chemistry, Washington University in St. Louis, Saint Louis, MO 63105, USA., Anuchapreeda S; Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.; Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand.; Cancer Research Unit of Associated Medical Sciences (AMS-CRU), Chiang Mai University, Chiang Mai 50200, Thailand.
Jazyk: angličtina
Zdroj: Polymers [Polymers (Basel)] 2024 Sep 02; Vol. 16 (17). Date of Electronic Publication: 2024 Sep 02.
DOI: 10.3390/polym16172498
Abstrakt: A targeted micellar formation of doxorubicin (Dox) and curcumin (Cur) was evaluated to enhance the efficacy and reduce the toxicity of these drugs in KG1a leukemic stem cells (LSCs) compared to EoL-1 leukemic cells. Dox-Cur-micelle (DCM) was developed to improve the cell uptake of both compounds in LSCs. Cur-micelle (CM) was produced to compare with DCM. DCM and CM were conjugated with two FLT3 (FMS-like tyrosine kinase)-specific peptides (CKR; C and EVQ; E) to increase drug delivery to KG1a via the FLT3 receptor (AML marker). They were formulated using a film-hydration technique together with a pH-induced self-assembly method. The optimal drug-to-polymer weight ratios for the DCM and CM formulations were 1:40. The weight ratio of Dox and Cur in DCM was 1:9. DCM and CM exhibited a particle size of 20-25 nm with neutral charge and a high %EE. Each micelle exhibited colloidal stability and prolonged drug release. Poloxamer 407 (P407) was modified with terminal azides and conjugated to FLT3-targeting peptides with terminal alkynes. DCM and CM coupled with peptides C, E, and C + E exhibited a higher particle size. Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells.
Databáze: MEDLINE
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