(472e) Nanoparticles Masquerade As ″self″ to Inhibit Phagocytosis

A major challenge for injecting particles or implanting biomaterials into the body is that they activate immune cells such as macrophages, the cells that normally function to clear invading pathogens. Interestingly, macrophages have a surface receptor mechanism which prevents them from phagocytosing our own “self” cells. During initial macrophage engulfment, macrophages recognize foreign and self targets because they both have antibodies or plasma complement proteins on their surface.  However, before the macrophage engulfs the target, self cells are checked for the presence of the surface protein CD47 which will bind to the macrophage receptor SIRPa (CD172), and we show that CD47-SIRPa interactions in cell-cell adhesion, with human macrophages in sparse culture, produce phagocytosis inhibition (Tsai & Discher, JCB 2008). Whether the CD47 interaction is functional with small targets of phagocytosis is unclear and relevant perhaps to nano-sized targets.  We show that CD47 coupled to a series of synthetic beads can inhibit uptake by macrophages. However, we need to test this interaction and observe how these results are consistent with in vivo systems. We are currently testing whether nanoparticles that have surface immobilized hCD47 or a portion of it will not be phagocytosed in nobese diabetic (NOD) mice, we believe that hCD47 will bind to this mSirpa strain and that could bring a better understanding of the interaction at a nanoscale.