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.
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Authors | Tatiana V Demina, Olga A Budkina, Gennadii A Badun, Nickolay S Melik-Nubarov, Holger Frey, Sophie S Müller, Jörg Nieberle, Irina D Grozdova |
Journal | Biomacromolecules
(Biomacromolecules)
Vol. 15
Issue 7
Pg. 2672-81
(Jul 14 2014)
ISSN: 1526-4602 [Electronic] United States |
PMID | 24926528
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antineoplastic Agents
- Micelles
- Polymers
- polyglycerol
- Polyethylene Glycols
- Doxorubicin
- Glycerol
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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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