ИСТИНА

Amphiphilic non-ionic block copolymers attract attention as bioactive agents. It is known that copolymers with intermediate hydrophobicity can induce MDR reversal in cancer cells and blood-brain barrier, while hydrophilic protect cells from mechanical stress. The present work was aimed to reveal structure-activity relationships in the series of non-ionic amphiphilic block copolymers containing propylene oxide, dimethylsiloxane or hydrocarbon radicals in their hydrophobic blocks and PEG or polyglycerol (PG) as hydrophilic blocks. Three biological effects are inherent for nearly all copolymers. Below CMC copolymers induce MDR reversal. At higher concentrations both hydrophilic and hydrophobic copolymers enhance cell viability. Further increase in polymer content leads to toxicity. Copolymer concentration sufficient for MDR reversal (CMDR) correlates with the polymer ability to accelerate flip-flop in model lipid bilayers, indicating that interaction of PPO or PDMS hydrophobic blocks with lipid bilayer of cellular membrane underlies MDR reversion. PG-based block copolymers do no exhibit cell supporting activity. The copolymers bearing linear PEG blocks are able to enhance cell survival. The polymers with long PEG chains are effective as unimers while relatively hydrophobic polymers acquire this property only in the form of micelles. The effect may result from PEG interaction with oligosaccharides of glycocalyx. Copolymers cytotoxicity was defined by their HLB and is mainly governed by formation of pores in cell membranes. To avoid the undesired support of cancer cells, PEG-containing copolymers should be used at concentrations close to CMDR. PG-based amphiphiles could be used as chemosensitizers in the full range of nontoxic concentrations above or equal to CMDR without any risk to enhance survival of cancer cells.