Erythrocyte‐Inspired Delivery Systems

Abstract

Herein recent progress in developing red blood cell (RBC)-inspired delivery systems is reviewed, with an emphasis on how our growing understanding of fundamental biological properties of natural RBCs has been applied in the design and engineering of these delivery systems. Specifically, progress achieved in developing carrier RBCs, a class of delivery vehicles engineered by directly loading natural RBCs with therapeutic agents, will be reviewed. Then alternative approaches to engineering synthetic vehicles through mimicking the mechanobiological and chemico-biological properties of natural RBCs will be considered. The synthesis and application of RBC membrane-derived vesicles, of which the natural RBC membranes are collected and directly utilized to prepare drug carriers, will then be discussed. Finally, a recent approach in engineering RBC membrane-camouflaged nanoparticle systems that combine advantages of natural RBCs and synthetic biomaterials will be highlighted. These developments indicate that RBC-inspired delivery systems will result in next-generation nanomedicine with extensive medical applications.

Nanobiotechnology for the Therapeutic Targeting of Cancer Cells in Blood

“…Residing in the same environment as macrophages and lymphocytes, RBCs evade the immune system by displaying selfantigens on their outer membrane. 50,64,109 RBC derivatives that incorporate self-antigens, such as CD47, 48 or a complete RBC membrane, 39,50,51 have shown reduced immunogenicity compared to naked particles. For instance, Gao et al 106 demonstrated a fourfold reduction in the uptake of gold nanoparticles (AuNP) coated with RBC membrane by macrophages in vitro.…”

“…120,124 Conjugation of various molecules, including antibodies, to RBC membranes can be accomplished through a biotin-avidin linkage. 50,103 In contrast to RBC biomimetic platforms that primarily seek to improve drug circulation time and biocompatibility, nanoparticles that mimic behaviors of platelets may not only extend the half-life of particles in blood but also bind CTCs with mechanisms similar to natural platelets. A platelet-mimetic approach for metastasis-targeted nanomedicine has been recently developed.…”

A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles

“…These hybrid particles called leukolike vectors (LLV) have similar function with leukocytes, it is able to prevent rapid clearance of phagocytic cells of the immune system; communicate with endothelial cells through receptor-ligand interaction; transport and release a payload across an inflamed reconstructed endothelium (Parodi et al, 2013). Similarly, Zhang et al developed an RBC-membrane-camouflaged polymeric nanoparticle platform (Hu et al, 2011(Hu et al, , 2012 (Figure 5), which elegantly united the advantage of natural RBCs and synthetic polymers. It successfully prevented RES system uptake without side effects and exhibited a long circulatory half-life as compared to PEG coating NPs (Luk & Zhang, 2015).…”

Red blood cell encapsulated optodes for the camouflaged monitoring of lithium levels in blood

“…[20][21][22][23][24][25][26] Assuming the RBC ghosts can one day be made from the patient's own blood, even longer lifetimes of up to days or weeks (as is with a normal RBC) can be expected. [26][27][28][29] Extended lifetime in the body is the exact characteristic that lithium optodes are lacking for meaningful TDM of lithium and it can be extrapolated that, if RBC ghosts containing drugs can evade uptake by creating a camouflaged exterior, then they can do the same for our optodes.…”

“…RBC ghosts are promising platforms for targeted drug delivery [20][21][22][23][24][25][26] because they allow for drugs to go unnoticed in the body's bloodstream; RBC ghosts act as a camouflaging sheath for their cargo and enable longer retention in the bloodstream before macrophage uptake or filtration occurs. [20][21][22][23][24][25][26] Assuming the RBC ghosts can one day be made from the patient's own blood, even longer lifetimes of up to days or weeks (as is with a normal RBC) can be expected.…”