Abstract
Dasatinib (DAS), a second-generation tyrosine kinase inhibitor, is highly effective in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, its clinical use is limited due to serious adverse effects. DAS can disrupt endothelial barrier integrity and increase endothelial permeability which may cause peripheral edema and pleural effusion. Albumin nanoparticles (NPs) as a drug carrier may serve as a useful tool for cell-selective drug delivery to reduce DAS-induced endothelial hyperpermeability and maintain endothelial barrier integrity. In this study, we reported that DAS-loaded NPs exhibited potent anti-leukemia efficacy as DAS alone. Importantly, albumin NPs as a drug carrier markedly reduced DAS-induced endothelial hyperpermeability by restraining the inhibition of Lyn kinase signaling pathway in endothelial cells. Therefore, albumin NPs could be a potential tool to improve anti-leukemia efficacy of DAS through its cell-selective effects.
Document Type
Article
Publication Date
7-6-2016
Digital Object Identifier (DOI)
https://doi.org/10.18632/oncotarget.10435
Funding Information
Chunling Dong is a recipient of the State Scholarship from China Scholarship Council.
Repository Citation
Dong, Chunling; Li, Bo; Li, Zhenyu; Shetty, Sreerama; and Fu, Jian, "Dasatinib-loaded Albumin Nanoparticles Possess Diminished Endothelial Cell Barrier Disruption and Retain Potent Anti-Leukemia Cell Activity" (2016). Internal Medicine Faculty Publications. 96.
https://uknowledge.uky.edu/internalmedicine_facpub/96
Notes/Citation Information
Published in Oncotarget, v. 7, no. 31, p. 49699-49709.
Licensed under a Creative Commons Attribution 3.0 License.