title: Dasatinib-loaded albumin nanoparticles possess diminished endothelial cell barrier disruption and retain potent anti-leukemia cell activity.
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.
authors.affiliation: Department of Respiratory Medicine, Second Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Human Anatomy, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Sreerama
authors.initials: S
authors.lastname: Shetty
authors.affiliation: Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY, USA.|Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Fu
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D002470:Cell Survival; D000069439:Dasatinib / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D008027:Light; D053758:Nanoparticles / Q000737:chemistry; D010539:Permeability; D011651:Pulmonary Artery / Q000166:cytology; D012542:Scattering, Radiation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D004337:Drug Carriers; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D000069439:Dasatinib
keywords: drug carrier; endothelial barrier; leukemia; nanoparticles; tyrosine kinase