Pharmaceutical Research

, Volume 20, Issue 2, pp 221–228

Phagocytosis and Phagosomal Fate of Surface-Modified Microparticles in Dendritic Cells and Macrophages

Article

DOI: 10.1023/A:1022271020390

Cite this article as:
Thiele, L., Merkle, H.P. & Walter, E. Pharm Res (2003) 20: 221. doi:10.1023/A:1022271020390

Abstract

Purpose. We compared cationic, polyamine-coated microparticles (MPs) and anionic, protein-coated MPs with respect to their phagocytosis and phagosomal fate in dendritic cells (DCs) and macrophages (MΦ).

Methods. Polystyrene MPs were surface modified by covalent coupling with fluorescein isothiocyanate-labeled polyamines or proteins. Phagocytosis of MP and the pH of their intracellular microenvironment was assessed in human-derived DCs and MΦ in a fluorescence plate reader. Visualization of MP phagocytosis in DCs was performed by transmission electron microscopy.

Results. Phagocytosis of bovine serum albumin-coated MPs was low with significant differences between DC and MΦ, whereas phagocytosis of IgG-coated MPs was significantly enhanced in both cell types. Phagocytosis of both particle types resulted in an acidified phagosomal microenvironment (pH 4.6-5.1). In contrast, cationic, polyamine-coated MPs were equally phagocytosed by DCs and MΦ to a high extent and showed lower degrees of acidification (pH 6.0-6.8) in the phagosomal microenvironment. Transmission electron microscopy examination demonstrated all phagocytosed particles to be surrounded by a phagosomal membrane, which was more tightly apposed to the surface of cationic MPs and more loosely to bovine serum albumin-coated MPs.

Conclusion. Phagocytosis of cationic, polyamine-coated MPs is suggested to lead to diminished phagosomal acidification. Thus, cationic MP are potential carriers that may display beneficial features for the intracellular delivery of immunomodulating therapeutics and their protection against lysosomal degradation.

dendritic cells macrophages surface-modified microparticles phagocytosis intracellular fate 

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  1. 1.Department of Applied BioSciencesSwiss Federal Institute of Technology Zurich (ETH)ZurichSwitzerland

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