Dasatinib-loaded albumin nanoparticles possess diminished endothelial cell barrier disruption and retain potent anti-leukemia cell activity
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Chunling Dong1,*, Bo Li2,*, Zhenyu Li3, Sreerama Shetty4, Jian Fu5,6
1Department of Respiratory Medicine, Second Hospital, Jilin University, Changchun, Jilin, P.R. China
2Department of Human Anatomy, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China
3Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA
4Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX, USA
5Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY, USA
6Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, USA
*These authors contributed equally to this work
Jian Fu, email: [email protected]
Keywords: tyrosine kinase, endothelial barrier, leukemia, drug carrier, nanoparticles
Received: May 23, 2016 Accepted: June 26, 2016 Published: July 06, 2016
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.
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