(526f) Drug Delivery Carriers Masquerade as ²self² to Avoid Body Clearance

Particle injected or surface implanted in the body are susceptible to recognition by the immune cells such as macrophage, which are responsible for the clearance of invading pathogens. However macrophage at the same time leave our own ²self² cells alone. The foreign versus self difference does not reside by steric repulsion by glycosylated proteins that have been mimicked using polymer PEG in drug delivery carriers. We have sought to address how macrophages specifically recognize self and to define its limits in systems from nano to micron scale systems by focusing on a cell-surface protein found on all of our cells. In the first stage of macrophage engulfment, the target objects are recognized with the deposition of antibodies or plasma complement proteins that binds to both foreign and self cells. However prior to macrophage engulfing its target, it checks for an identification of self cells, the protein CD47. Initially we demonstrate that 100 aa extracellular component of CD47 when coupled to synthetic particles is sufficient in reducing uptake. The potency of CD47 is not limited to micron sized particles but applies to nano-sized particle because of the inhibitory effect when CD47 is recognized by the receptor SIRPα on macrophages. By exploiting the bodies own system of distinguishing ²self² from foreign using the latest polymer PEG drug delivery carriers coupled with CD47 lead to effective delivery of drug and genetic material to its intended targets by avoiding the immune system.