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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.
AuthorsTatiana V Demina, Olga A Budkina, Gennadii A Badun, Nickolay S Melik-Nubarov, Holger Frey, Sophie S Müller, Jörg Nieberle, Irina D Grozdova
JournalBiomacromolecules (Biomacromolecules) Vol. 15 Issue 7 Pg. 2672-81 (Jul 14 2014) ISSN: 1526-4602 [Electronic] United States
PMID24926528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Micelles
  • Polymers
  • polyglycerol
  • Polyethylene Glycols
  • Doxorubicin
  • Glycerol
Topics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
  • Antineoplastic Agents (pharmacology)
  • Cell Survival (drug effects)
  • Doxorubicin (pharmacology)
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Glycerol (pharmacology)
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • K562 Cells
  • MCF-7 Cells
  • Micelles
  • Polyethylene Glycols (pharmacology)
  • Polymers (pharmacology)

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