Towards a Better Understanding of the Interaction between Phagocytic Immune Cells and Synthetic Particulates

Abstract

Particulate technology has transformed the field of diagnostic and therapeutic medicine due to the ability of particulates to provide better contrast in various imaging modalities and improve the targeting of therapeutic agents to specific tissues in the body. Several nano and micro-particles have found applications in the clinic, and it is expected that many humans are likely to come in contact with such systems in their lifetime. Once administered in vivo, these particulates are captured by phagocytic immune cells, which surveil the host system for foreign substances. The process of recognition and internalization of foreign substances may lead to cellular changes in phagocytic immune cells. A few studies have suggested that based on the physicochemical properties of the diagnostic or therapeutic particles, phagocytic immune cells may be activated towards an inflammatory or anti-inflammatory phenotype. Additionally, uptake of particles may alter cytokine secretion, chemotaxis behavior, oxidative burst, and nitric oxide generation in these cells. However, the effects of particulate uptake on the primary functions of a phagocytic immune cell, which are the internalization of foreign substances and neutralization of pathogens, remains poorly addressed. In this work, we determine how the uptake of particles changes an immune cell s phagocytic ability and bactericidal activity. Using various phagocytic cell types and cargo-free particles, we demonstrate that particle uptake results in the enhancement of the phagocytic capacity of immune cells. We show that the increased uptake is not a result of cellular activation or cellular heterogeneity; instead, the first phagocytic event appears to prime the cell for subsequent phagocytosis. A consequence of the enhanced uptake ability is that particulate-laden-immune cells show faster clearance of bacteria both in vitro and in vivo...