(596c) The Effect of Particle Physico-Chemical Properties on Phagocytosis

The effect of particle physico-chemical properties on phagocytosis
Anusha Garapaty¹, Julie A.Champion¹, (1) School ofChemical and Biomolecular Engineering,
Georgia Institute of Technology, Atlanta, GA

The tunability of polymeric particle properties makes them attractive for a wide range of applications in drug delivery, imaging and diagnostics. Their physico-chemical properties such as size, shape, surface chemistry and stiffness can be altered to influence their interactions with cells. It has become imperative to establish a correlation between these physico-chemical properties and biological behavior to design targeted delivery systems. During these delivery applications, particles introduced into the body interact with macrophages of the reticuloendothelial system. These macrophages rapidly clear them through a process known as phagocytosis thus limiting their potential in biomedical applications involving either phagocytic inhibition or macrophage targeting.

The influence of material parameters size, shape and mechanical stiffness on phagocytosis has been established previously [1-3]. However, the combinatorial effects of these material biophysical parameters on phagocytosis is still unknown. Our objective in this work is to understand how the combined effects of particle physico-chemical properties size, shape and stiffness affect the process of phagocytosis using particles which can be independently tuned in each of these properties while keeping the chemistry constant.

Tunable particles have been fabricated by the development of a template based layer-by-layer (LbL) assembly process. Polystyrene particles of varied sizes were chosen as the template. Shape is imparted to the polystyrene particles by heat liquefaction while stretching. The polystyrene template particles are adsorbed with polyelectrolytes poly (vinyl pyrrolidone) (PVP), poly (ethyleneimine) (PEI), and poly (acrylic acid) (PAA) by LbL self assembly. Mechanical stiffness can be varied either by maintaining the solid template core or by making hollow capsule particles through tetrahydrofuran treatment and thiol crosslinking of the polyelectrolyte layers. To study specific Fc interaction with macrophages, the particles were coated with IgG antibody. Our results show that for a spherical shape, when the size is altered cores are internalized slightly more than corresponding capsules during phagocytosis. However, when the shape is altered to a rod for a particular size, capsules exhibit enhanced internalization compared to corresponding cores. These particles thus demonstrate that shape and stiffness play a crucial role in tuning the specificity of IgG functionalized particle interactions with macrophages. This novel polymer particle platform can also be further extended to functionalization of active ligands for phagocytic inhibiton or modulation of macrophage activity and phenotype in immunological therapeutic applications.

References

1. Beningo, K.A. and Y.-l. Wang, Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target. Journal of cell science, 2002. 115(4): p. 849-856.

2. Champion, J.A. and S. Mitragotri, Role of target geometry in phagocytosis. Proceedings of the National Academy of Sciences of the United States of America, 2006. 103(13): p. 4930-4934.

3. Champion, J.A., A. Walker, and S. Mitragotri, Role of particle size in phagocytosis of polymeric microspheres. Pharmaceutical research, 2008. 25(8): p. 1815-1821.