Nonionic amphiphiles and particularly block copolymers of ethylene oxide and propylene oxide
(Pluronics) cause pronounced chemosensitization of tumor cells that exhibit multiple resistance to
antineoplastic drugs. This effect is due to inhibition of P-glycoprotein (P-gp) responsible for drug efflux.
It was suggested that the inhibition of P-gp might be due to changes in its lipid surrounding. Indeed, high
dependence of P-gp activity on the membrane microviscosity was demonstrated [Regev et al. (1999) Eur.
J. Biochem. 259, 18−24], suggesting that the ability of Pluronics to affect the P-gp activity is mediated
by their effect on the membrane structure. We have found recently that adsorption of Pluronics on lipid
bilayers induced considerable disturbance of the lipid packing [Krylova et al. (2003) Chemistry
9, 3930−3936]. In the present paper, we studied 19 amphiphilic copolymers, including newly synthesized
hyperbranched polyglycerols, Pluronic and Brij surfactants, for their ability to accelerate flip-flop and
permeation of antitumor drug doxorubicin (DOX) in liposomes. It was found that not only bulk
hydrophobicity but also the chemical microstructure of the copolymer determines its membrane disturbing
ability. Copolymers containing polypropylene oxide caused higher acceleration of flip-flop and DOX
permeation than polysurfactants containing aliphatic chains. The effects of copolymers containing
hyperbranched polyglycerol “corona” were more pronounced, as compared to the copolymers with linear
poly(ethylene oxide) chains, indicating that a bulky hydrophilic block induces additional disturbances in
the lipid bilayer. A good correlation between the copolymer flippase activity and a linear combination of
copolymer bulk hydrophobicity and the van der Waals volume of its hydrophobic block was found. The
relationship between the structure of a copolymer and its ability to disturb lipid membranes presented in
this paper may be useful for the design of novel amphiphilic copolymers capable of affecting the activity
of membrane transporters in living cells.
The formation of biominerals by living organisms is governed by the cooperation of soluble and insoluble macromolecules with peculiar interfacial properties. To date, most of the studies on mineralization processes involve model systems that only account for the existence of one organic matrix and thus disregard the interaction between the soluble and insoluble organic components that is crucial for a better understanding of the processes taking place at the inorganic-organic interface. We have set up a model system composed of a matrix surface, namely, a self-assembled monolayer (SAM), and a soluble component, hyperbranched polyglycerol. The model mineral calcium carbonate displays diverse polymorphism. It could be demonstrated that the phase selection of calcium carbonate is controlled by the cooperative interaction of the SAM and hyperbranched polyglycerol of different molecular weights (M(n) = 500-6000 g/mol) adsorbed to the SAM. Our studies showed that hyperbranched polyglycerol is adsorbed to polar as well as to nonpolar SAMs. This effect can be related to its highly flexible structure and its amphiphilic character. The adsorption of hyperbranched polyglycerol to the SAMs with different surface polarities resulted in the formation of aragonite for alkyl-terminated SAMs and no phase selection for carboxylate-terminated SAMs.
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