Virosomes can enter cells by non-phagocytic mechanisms

Abstract

Phagocytosis of fine particles (1 μm) by macrophages is a ligand-receptor–mediated, actin-based process, whereas the entering of smaller particles (≤ 0.2 μm) in macrophages occurs also by other mechanisms. Virosomes with a diameter of 0.12–0.18 μm are widely used as carrier systems for drugs, vectors, and plasmids in cancer therapy or for vaccines. We investigated their interactions with airway cells, in particular penetration into monocyte-derived macrophages. The microscopic analysis of phagocytic cells incubated with virosomes and polystyrene particles showed that virosomes and particles penetrated cells even in the presence of cytochalasin D, a drug inhibiting actin-based phagocytosis. The charge of the virosomes and particles did not influence their penetration. Also, different inhibitors of endocytotic pathways did not prevent the particles and virosomes from penetrating into the cells. Additionally, to study the ability of virosomes to overcome the epithelial airway barrier, a triple cell co-culture model composed of epithelial cells, monocyte-derived macrophages and dendritic cells of the respiratory tract was used. We found virosomes and polystyrene particles in both populations of antigen-presenting cells, monocyte-derived macrophages, and dendritic cells, in the latter even if they were not directly exposed. In conclusion, virosomes are readily taken up by monocyte-derived macrophages, both by conventional phagocytosis and by actin-independent mechanisms. Further, they can penetrate the airway barrier and reach resident dendritic cells. Therefore, virosomes are promising vaccine candidates.

Keywords::

• Virosomes
• polystyrene particles
• macrophages
• dendritic cells
• epithelial airway model
• laser scanning microscopy

Acknowledgments

The authors are grateful to B. Tschirren and S. Frank for their excellent technical assistance. We thank Dr. Reinhard Glück for stimulating discussions. This work was supported by the Swiss National Science Foundation (Nr. 32-65352.01 and 3100A0_118420), the Swiss Agency for the Environment, Forests and Landscape, and the Silva Casa Foundation.

Declaration of interest: The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper.