title: Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia.
abstract: The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Robert C
authors.identifier: 0000-0002-5812-583X
authors.initials: RC
authors.lastname: Deller
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.|Bristol Institute for Transfusion Sciences, NHS Blood and Transplant , Bristol BS34 7QH, United Kingdom.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Diamanti
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Morrison
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Reilly
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Ede
authors.affiliation: School of Physics, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Richardson
authors.affiliation: School of Biochemistry, University of Bristol , Bristol BS8 1TH, United Kingdom.|Bristol Centre for Functional Nanomaterials, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Kristian
authors.initials: K
authors.lastname: Le Vay
authors.affiliation: School of Physics, University of Bristol , Bristol BS8 1TH, United Kingdom.|Bristol Centre for Functional Nanomaterials, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Collins
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.|Bristol Institute for Transfusion Sciences, NHS Blood and Transplant , Bristol BS34 7QH, United Kingdom.
authors.forename: Allison
authors.initials: A
authors.lastname: Blair
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Perriman
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D012997:Solvents / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D004655:Emulsions; D008823:Micelles; D011108:Polymers; D012717:Sesquiterpenes; D012997:Solvents; C002669:parthenolide
keywords: acute lymphoblastic leukemia (ALL); micelle; nanoparticle; parthenolide; pluronic; poloxamer