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Phagocytosis and phagosomal fate of surface-modified microparticles in dendritic cells and macrophages

Lars Thiele1, Hans P Merkle, Elke Walter

  • 1Department of Applied BioSciences, Swiss Federal Institute of Technology Zurich (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

Pharmaceutical Research
|March 15, 2003
PubMed
Abstract

Insights

Cationic microparticles (MPs) are readily phagocytosed by dendritic cells (DCs) and macrophages (Mphi), leading to less acidic phagosomes. This suggests cationic MPs are promising carriers for delivering therapeutics and protecting them from degradation.

Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Immunology

Background:

  • Microparticles (MPs) are investigated for drug delivery.
  • Surface charge influences particle uptake and intracellular fate.

Purpose of the Study:

  • Compare phagocytosis and phagosomal fate of cationic, polyamine-coated MPs and anionic, protein-coated MPs in dendritic cells (DCs) and macrophages (Mphi).

Main Methods:

  • Surface modification of polystyrene MPs with polyamines or proteins.
  • Assessment of MP phagocytosis and phagosomal pH in human DCs and Mphi using a fluorescence plate reader.
  • Visualization of MP phagocytosis in DCs via transmission electron microscopy.

Main Results:

  • Anionic, protein-coated MPs showed low (BSA) to enhanced (IgG) phagocytosis with significant cell-type differences.
  • Both anionic and cationic MPs resulted in phagosomal acidification (pH 4.6-5.1).
  • Cationic, polyamine-coated MPs were highly phagocytosed by both cell types, with reduced phagosomal acidification (pH 6.0-6.8).

Conclusions:

  • Cationic MPs lead to diminished phagosomal acidification.
  • Cationic MPs show potential as carriers for intracellular delivery of immunomodulating therapeutics.
  • Cationic MPs may protect therapeutics from lysosomal degradation.

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