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Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells.

Lena Kastl1, Daniel Sasse, Verena Wulf

  • 1Fachbereich Physik, Philipps-Universität Marburg, Renthof 7, 35037 Marburg, Germany.

ACS Nano
|July 6, 2013
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Summary

Polyelectrolyte multilayer (PEM) capsules enter cells via a multi-step process involving electrostatic interactions, phagocytic cup formation, and lipid-raft-mediated macropinocytosis, ultimately localizing in phagolysosomes.

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Nanotechnology

Background:

  • Polyelectrolyte multilayer (PEM) capsules are promising nanocarriers for drug delivery.
  • Understanding their cellular uptake is crucial for developing effective therapeutic systems, particularly for cancer treatment.

Purpose of the Study:

  • To investigate the internalization pathway and intracellular fate of PEM capsules.
  • To elucidate the mechanisms governing PEM capsule uptake in mammalian cells.

Main Methods:

  • Co-localization studies with endocytic markers.
  • Inhibition of endocytic pathways using chemical agents.
  • Confocal and electron microscopy for uptake quantification and characterization.

Main Results:

  • PEM capsules co-localized with lipid rafts and phagolysosomes, but not other endocytic vesicles.
  • Uptake was slightly sensitive to electrostatic interactions, independent of clathrin/caveolae, but dependent on cholesterol-rich domains and acidification.
  • Cellular uptake involved phagocytic cup formation, increased mitochondria, and perinuclear localization.

Conclusions:

  • PEM capsule internalization is a sequential process initiated by electrostatic adsorption.
  • Phagocytic engulfment and lipid-raft-mediated macropinocytosis are key mechanisms.
  • Capsules are sorted to heterophagolysosomes, indicating a specific intracellular fate.