Red blood cells membrane-derived nanoparticles: Applications and key challenges in their clinical translation

Cellular membrane-derived nanoparticles, particularly of red blood cells (RBCs), represent an emerging class of drug delivery systems. The lack of nucleus and organelles in these cells makes them easy to process and empty out intracellular contents. The empty vesicle membranes can then be either used as a coating on nanoparticles or can be reassembled into a nanovesicle. Engineered RBCs membrane has unique ability to retain its lipid bilayer architecture with host's proteins during top-down approach, thus allowing it to form stable nanoformulations mimicking RBCs stealth properties. In addition, its core-shell structure allows loading of different drug molecules, and its surface chemistry can be manipulated by facile conjugation with ligands on the shell. The remarkable ability of RBCs membrane to fuse with membranes of other cells enables the formation of hybrid nanovesicles. In this review, we highlight the biomedical applications of such vesicles and discuss the potential challenges related to its clinical translation. Although nano-RBCs retain much of the host's proteins, which may give an edge over synthetic nanoparticles in terms of lower immunogenicity, its production at industrial level is more challenging. This review gives the critical analysis of barriers involved in the translation of RBCs-derived nanoparticles from preclinical to clinical level. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.