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The relationship between the block architecture of copolymers consisting of poly(ethylene oxide) and poly(propylene oxide), their ability to induce disturbances in lipid bilayer membranes and cause chemosensitization of tumor cells was investigated. It was found that the ability of copolymers to induce disturbances in model membranes composed of egg lecithin increased with the volume of their hydrophobic blocks. Extremely high channel-forming and flippase activity was observed for the copolymer possessing a brush-like structure. The addition of cholesterol into lipid bilayers reduced the effects induced by copolymers, however, to different extents. The sensitivity of copolymer-induced effects to the addition of cholesterol increased with the growth of the critical packing parameter, which was estimated as a ratio of the volume of the whole copolymer chain to the water-accessible area of its polar headgroup and the distance between the hydrophilic and hydrophobic edges of the molecule. The comparison of the copolymers effect on multi-drug resistant human breast adenocarcinoma MCF7/DOX cells showed that two block copolymers RPE caused maximal chemosensitization, compromising between the shape of the amphiphile and the volume of its hydrophobic block. |
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