Nanoparticle uptake: The phagocyte problem

• Diverse populations of different macrophages very effectively clear nanomaterials using specific and non-specific uptake mechanisms.
• Nanomaterials are very efficiently scavenged from circulating blood and tissues by macrophages resident in tissue and filtration organs (MPS system), severely limiting particle targeting.
• To avoid rapid uptake, clearance and to improve targeting, nanomaterials that avoid both specific and non-specific macrophage recognition must be developed to improve intra- and extra-cellular targeting.
• Long-term residence of non-degradable systems within macrophages in clearance organs poses a unique challenge and could initiate inflammatory mechanisms.

SummaryPhagocytes are key cellular participants determining important aspects of host exposure to nanomaterials, initiating clearance, biodistribution and the tenuous balance between host tolerance and adverse nanotoxicity. Macrophages in particular are believed to be among the first and primary cell types that process nanoparticles, mediating host inflammatory and immunological biological responses. These processes occur ubiquitously throughout tissues where nanomaterials are present, including the host mononuclear phagocytic system (MPS) residents in dedicated host filtration organs (i.e., liver, kidney spleen and lung). Thus, to understand nanomaterials exposure risks it is critical to understand how nanomaterials are recognized, internalized, trafficked and distributed within diverse types of host macrophages and how possible cell-based reactions resulting from nanomaterial exposures further inflammatory host responses in vivo. This review focuses on describing macrophage-based initiation of downstream hallmark immunological and inflammatory processes resulting from phagocyte exposure to and internalization of nanomaterials.

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