Bio-degradable nanoparticles (NPs) have several utilizations as drug delivery vehicles due to their acceptable bio-availability, lower toxicity, potency for encapsulation and controlled release. Moreover, the interaction of the NPs with the macrophages of the reticuloendothelial system (RES) may decrease NPs efficacy for medical purposes. The surface of NPs is conventionally neutralized with the molecules such as poly(ethylene glycol) (PEG), as one of the most widely applied stealth polymers, in order to restrict the NPs clearance through the RES system. In fact, these molecules exhibit resistance to RES clearance and protein adsorption. It is unfortunate that modifying the PEG has some shortcomings, like problems in the synthesis as well as correlation to the immune reaction. The CD47 receptor has been well known as a ‘don’t-eat-me’ molecule on the self-- cells' surface. Therefore, the receptor will inhibit phagocytosis via binding to its ligand that is known as the signal regulatory protein α (SIRP-α). Moreover, the CD47 receptor, as one of the biomimetic substances, or its derivative peptides, have been used recently on the surface of nanoparticles to inhibit phagocytosis and increase the NPs retention time in the blood circulation.

Therefore, this review study examined the CD47 receptor and its role in the immune system as well as the use of the CD47 receptor in coating NPs to increase their retention time in the blood circulation.