title: Cytotoxicity and chemosensitizing activity of amphiphilic poly(glycerol)-poly(alkylene oxide) block copolymers.
abstract: All polymeric chemosensitizers proposed thus far have a linear poly(ethylene glycol) (PEG) hydrophilic block. To testify whether precisely this chemical structure and architecture of the hydrophilic block is a prerequisite for chemosensitization, we tested a series of novel block copolymers containing a hyperbranched polyglycerol segment as a hydrophilic block (PPO-NG copolymers) on multi-drug-resistant (MDR) tumor cells in culture. PPO-NG copolymers inhibited MDR of three cell lines, indicating that the linear PEG can be substituted for a hyperbranched polyglycerol block without loss of the polymers' chemosensitizing activity. The extent of MDR reversal increased with the polymers affinity toward the cells and the expression level of P-glycoprotein. In contrast with Pluronic L61, which increases viability of tumor cells in the absence of drugs, PPO-NG chemosensitizers are completely devoid of this property undesired in cancer therapy, making them promising candidates for application as novel MDR reversal agents.
authors.affiliation: Chemistry Department, Lomonosov Moscow State University , Vorobiovy Gory, Moscow 119991, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Demina
authors.forename: Olga A
authors.initials: OA
authors.lastname: Budkina
authors.forename: Gennadii A
authors.initials: GA
authors.lastname: Badun
authors.forename: Nickolay S
authors.initials: NS
authors.lastname: Melik-Nubarov
authors.forename: Holger
authors.initials: H
authors.lastname: Frey
authors.forename: Sophie S
authors.initials: SS
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Nieberle
authors.forename: Irina D
authors.initials: ID
authors.lastname: Grozdova
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005990:Glycerol / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D061986:MCF-7 Cells; D008823:Micelles; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; C043941:polyglycerol; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005990:Glycerol