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Effect of polycation nanostructures on cell membrane permeability and toxicity

The interaction of nanometric synthetic materials with cell membranes is one of the key factors determining their possible cytotoxicity. This work investigated the interaction of polycation nanostructures with lipid and cellular membranes. The nanostructures (polymer micelles) were formed in aqueous...

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Published in:Environmental science. Nano 2022-02, Vol.9 (2), p.72-713
Main Authors: Wytrwal-Sarna, Magdalena, Knobloch, Paulina, Lasota, S awomir, Michalik, Marta, Nowakowska, Maria, Kepczynski, Mariusz
Format: Article
Language:English
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Summary:The interaction of nanometric synthetic materials with cell membranes is one of the key factors determining their possible cytotoxicity. This work investigated the interaction of polycation nanostructures with lipid and cellular membranes. The nanostructures (polymer micelles) were formed in aqueous media as a result of the self-assembly of strong amphiphilic polycations containing hydrophobic alkyl groups of various lengths. The effect of alkyl length on micellization and its influence on the physicochemical properties and biological activity of the polycations were analyzed. Next, the cytotoxicity of the polycations was assessed using human skin fibroblasts (HSFs). The results show that the ability of the polycations to form pores in biomembranes decreases with the length of the attached alkyl groups. The polycations substituted with short alkyl groups were the most cytotoxic, which correlates well with their high capacity to open pores in biomembranes. However, they can perforate the fibroblast plasma membrane at non-toxic concentrations. Overall, our results show that the observed trends in cytotoxicity cannot be fully explained within simple interactions between polycationic micelles and cell membranes. A relationship does, however, seem to exist between polycation membrane activity (pore formation) and its cytotoxicity. Amphiphilic polycations with quaternary ammonium groups show a strong tendency to porate lipid membranes. The polycations with a high capacity to open pores in biomembranes are the most cytotoxic to cells.
ISSN:2051-8153
2051-8161
DOI:10.1039/d1en01156a