Research Paper Volume 12, Issue 7 pp 6018—6029
Reversal of multidrug resistance in leukemia cells using a transferrin-modified nanomicelle encapsulating both doxorubicin and psoralen
- 1 Department of Pediatrics, Rizhao People’s Hospital, Shandong, China
received: October 23, 2019 ; accepted: March 2, 2020 ; published: April 7, 2020 ;https://doi.org/10.18632/aging.102992
How to Cite
Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
To ameliorate multidrug resistance (MDR) observed in leukemia cells, nanomicelles modified by transferrin (Tf-M-DOX/PSO), coencapsulating doxorubicin (DOX) and psoralen (PSO), were designed, synthesized and tested in K562 and doxorubicin-resistant K562 (K562/DOX) cells. In vitro drug release kinetics for constructed nanomicelles were measured using high-performance liquid chromatography. Characterization of the produced nanomicelles was completed using transmission electron microscopy and dynamic light scattering. Uptake of the nanomicelles in K562 cells was investigated using both confocal microscopy and flow cytometry. Apoptosis levels as well as the expression of glycoprotein (P-gp) were analyzing by western blotting and flow cytometry. Cellular cytotoxicity resulting from the exposure of nanomicelles was evaluated using MTT assays. The nanomicelles all showed mild release of DOX in PBS solution. In K562/DOX cells, Tf-M-Dox/PSO exhibited higher uptake compared to the other nanomicelles observed. Furthermore, cellular cytotoxicity when exposed to Tf-M-Dox/PSO was 2.8 and 1.6-fold greater than observed in the unmodified DOX and Tf-nanomicelles loaded with DOX alone, respectively. Tf-M-Dox/PSO strongly increased apoptosis of K562/DOX cells. Finally, the reversal of the drug resistance when cells are exposed to Tf-M-DOX/PSO was associated with P-gp expression inhibition. The Tf-M-Dox/PSO nanomicelle showed a reversal of MDR, with enhanced cellular uptake and delivery release.