(704f) A Marker of ²self ² Protein On Beads Inhibits Clearance in Vitro and In Vivo

A major challenge to the injection of particles or implantation of biomaterials is that they activate macrophages, which normally function to clear foreign pathogens. Interestingly, macrophages have at least one surface receptor mechanism which inhibits them in phagocytosing ²self² cells. During initial macrophage engulfment, macrophages recognize all targets because they everything adsorbs antibodies or plasma proteins such as complement on their surface. However, before the macrophage engulfs the target, self cells are checked for the presence of the surface protein CD47. CD47 is recognized by the receptor SIRPα on macrophages which inhibits phagocytosis, and when we attach a 100 aa extracellular component of CD47 to micro- and nano-sized particle, we demonstrate, in vitro, that this sufficient to inhibit phagocytosis of these small particles. Now we are focusing our efforts on understanding how these results function in vivo. We are currently testing whether nanoparticles that have surface immobilized hCD47 will be phagocytosed or not in nobese diabetic (NOD) mice, because we believe human-CD47 will bind to it counter-receptor SIRPα in this particular mouse strain. By controlling the response of the immune system, we aim to trick the body into believing that foreign particles are actually ²self², and that this will lead to better biocompatibility and more efficient drug delivery.