Complement-dependent uptake of nanoparticles by blood phagocytes: brief overview and perspective

Immune recognition and uptake of nanoparticles remain the hot topic in nanomedicine research. Complement is the central player in the immune recognition of engineered nanoparticles. Here, we summarize the accumulated knowledge on the role of complement in the interactions of nanomaterials with blood phagocytes. We describe the interplay between surface properties, complement opsonization, and immune uptake, primarily of iron oxide nanoparticles. We discuss the rigor of the published research and further identify the following knowledge gaps: 1) the role of complement in the variability of uptake of nanomaterials in healthy and diseased subjects, and 2) modulation of complement interactions to improve the performance of nanomaterials. Addressing these gaps is critical to improving translational chances of nanomaterials for drug delivery and imaging applications.