Macrophages as Targets and Mediators in the Transport of Nanotherapeutics
34 Pages Posted: 19 Jun 2019 Publication Status: Review Complete
More...Abstract
Macrophages line the walls of microvasculature, extending processes into the blood flow to capture intruders, including nanoparticles. Here, using mesoporous silica or silicon particles, we show the interplay between macrophages and nanomaterial from initial uptake to intracellular trafficking along microtubules, to intercellular trafficking of material to neighboring cells. Transfer of materials between cells includes robust transfer of nanoparticles and cargo from macrophages to cancer cells in cytoplasmic bridges, coined tunneling nanotubes (TNT), and in thick, adherent connections with elaborate points of connection between cells. Both direct administration of nanoparticles and adoptive transfer of nanoparticle-loaded splenocytes in mice results in abundant localization of nanomaterials within macrophages 24 hours post injection. The relevance of macrophages as natural targets of nanomaterials and as significant regulators of the tumor microenvironment arises as an overlooked key-consideration when designing nano therapeutics for optimal drug delivery and therapeutic benefit.
Keywords: macrophage, doxorubicin, cancer, intercellular transport, mesoporous silica or silicon particle, tunneling nanotubes
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