title: Influence of amphiphilic block copolymer induced changes in membrane ion conductance on the reversal of multidrug resistance.
abstract: Block copolymers are able to reverse multidrug resistance (MDR) of tumor cells by a yet unknown mechanism. The drug efflux system's direct and indirect inhibition mediated by polymer P-glycoprotein (Pgp) interactions or adenosine triphosphate (ATP) depletion, respectively, may be involved in MDR reversal as well as damage to the membrane barrier caused by polymer insertion into the membrane. To test the latter hypothesis, cellular drug accumulation was monitored in the presence of both overexpressed fluorescently labeled Pgp and different block copolymers. Therefore, a new triblock copolymer (poly(ethylene oxide)- block-poly(hexafluoropropylene oxide)- block-poly(ethylene oxide)) was designed and synthesized by combined polymerization and polymer analogous reaction. Its administration induced drug uptake, whereas control cells with high Pgp expression levels showed no drug accumulation. Drug uptake was even more pronounced in the presence of another triblock copolymer: (poly(perfluorohexylethyl methacrylate)- block-poly(ethylene oxide)- block-poly(perfluorohexylethyl methacrylate). The latter polymer's lack of ionophoric activity suggests that ion transport facilitation by polymers is not a determinative factor for MDR reversal.
authors.affiliation: Johannes Kepler Universitat, Fachbereich Physik, Institut fur Biophysik, Altenbergerstrasse 69, 4040 Linz, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Sommer
authors.forename: Sergej
authors.initials: S
authors.lastname: Kaiser
authors.forename: Oxana O
authors.initials: OO
authors.lastname: Krylova
authors.forename: Jörg
authors.initials: J
authors.lastname: Kressler
authors.forename: Peter
authors.initials: P
authors.lastname: Pohl
authors.forename: Karsten
authors.initials: K
authors.lastname: Busse
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011108:Polymers; D000255:Adenosine Triphosphate