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Controlled Cellular Delivery of Amphiphilic Cargo by Redox‐Responsive Nanocontainers

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 r...

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Detalles Bibliográficos
Autores principales: de Vries, Wilke C., Kudruk, Sergej, Grill, David, Niehues, Maximilian, Matos, Anna Livia Linard, Wissing, Maren, Studer, Armido, Gerke, Volker, Ravoo, Bart Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918114/
https://www.ncbi.nlm.nih.gov/pubmed/31871866
http://dx.doi.org/10.1002/advs.201901935
Descripción
Sumario: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, C(SS)LV) with a homogeneous distribution of each lipid. Host–guest‐mediated self‐assembly of a cystamine‐crosslinked polymer shell on these C(SS)LV produces polymer‐shelled liposomal vesicles (P(SS)C(SS)LV) with the unique feature of a redox‐sensitive C(SS)LV core and reductively degradable polymer shell. P(SS)C(SS)LV show high stability and a redox‐sensitive release of the amphiphilic cargo. Live cell experiments reveal that the novel P(SS)C(SS)LV 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, P(SS)C(SS)LV represent a highly efficient system to transport lipid‐like amphiphilic cargo into the intracellular environment.