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Controlled Cellular Delivery of Amphiphilic Cargo by Redox-Responsive Nanocontainers.

ABSTRACT: The specific transport of amphiphilic compounds such as fluorescently labeled phospholipids into cells is a prerequisite for the analysis of highly dynamic cellular processes involving these molecules, e.g., the intracellular distribution and metabolism of phospholipids. However, cellular delivery remains a challenge as it should not affect the physiological integrity and morphology of the cell membrane. To address this, polymer nanocontainers based on redox-responsive cyclodextrin (CD) amphiphiles are prepared, and their potential to deliver fluorescently labeled phospholipids to intracellular membrane compartments is analyzed. It is shown that mixtures of reductively degradable cyclodextrin amphiphiles and different phospholipids form liposome-like vesicles (CD-lipid vesicles, CSSLV) with a homogeneous distribution of each lipid. Host-guest-mediated self-assembly of a cystamine-crosslinked polymer shell on these CSSLV produces polymer-shelled liposomal vesicles (PSSCSSLV) with the unique feature of a redox-sensitive CSSLV core and reductively degradable polymer shell. PSSCSSLV show high stability and a redox-sensitive release of the amphiphilic cargo. Live cell experiments reveal that the novel PSSCSSLV are readily internalized by primary human endothelial cells and that the reductive microenvironment of the cells' endosomes triggers the release of the amphiphilic cargo into the cytosol. Thus, PSSCSSLV represent a highly efficient system to transport lipid-like amphiphilic cargo into the intracellular environment.

SUBMITTER: de Vries WC

PROVIDER: S-EPMC6918114 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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