**4. The applications of red cell membrane in drug delivery systems and biosensors**

RCM-coated nanoparticles, also called RC-camouflaged nanoparticles, have been developed for drug delivery system since they were devised by Zhang and his group in 2011. It was found that immune evasive properties of RCM-coated nanoparticles are superior to conventional nanoparticles. The membrane proteins confer the advantages of the immune avoidance properties described in Section 2. RCM coating has been applied to various core nanoparticles such as gold, poly(lactic-coglycolic acid) (PLGA), silica, and iron oxide nanoparticles [30]. Also, RCM can be utilized as permselective filter for glucose biosensor taking advantage of GLUT on RCM [9].

## **4.1 Drug delivery with red cell membrane-coated nanoparticles**

In drug delivery system related with nanomaterial, long-term circulation of nanoparticles in vivo is one of the most important characteristics because various immune responses clear the foreign molecules in the body and blood [31]. Especially, MPS and CS are major immune systems eliminating drug delivery carriers. Conventionally, to evade the immune systems, the drug carriers are functionalized with polyethylene glycol (PEG) which slows clearance in blood and avoids non-specific binding of blood proteins [32, 33]. In our body, however, there is an anti-PEG immunological response which removes PEGylated nanoparticles [34]. By contrast, the RCM-coated nanoparticles showed prolonged circulation in blood. The result is exactly attributed to membrane receptors and cell adhesion molecules, which were abundant and diverse on RCM. In this regard, the immune evasive properties of RCM-functionalized nanomaterials have great potential as clinical drug delivery carriers. In particular, it is researched that the RCM-functionalized nanoparticles showed good dispersion stability in serum and great biodistribution in mice model up to 72 h (**Figure 7**) [7]. Indeed, it is demonstrated that the RCM inhibits macrophage uptake. RCM-coated gold nanoparticles showed ~4 times higher immune evasive properties than bare gold nanoparticles [8].
