Erythrocyte nanovesicles: Biogenesis, biological roles and therapeutic approach: Erythrocyte nanovesicles

Abstract

Nanovesicles (NVs) represent a novel transporter for cell signals to modify functions of target cells. Therefore, NVs play many roles in both physiological and pathological processes. This report highlights biogenesis, composition and biological roles of erythrocytes derived nanovesicles (EDNVs). Furthermore, we address utilization of EDNVs as novel drug delivery cargo as well as therapeutic target. EDNVs are lipid bilayer vesicles rich in phospholipids, proteins, lipid raft, and hemoglobin. In vivo EDNVs biogenesis is triggered by an increase of intracellular calcium levels, ATP depletion and under effect of oxidative stress conditions. However, in vitro production of EDNVs can be achieved via hypotonic treatment and extrusion of erythrocyte. NVs can be used as biomarkers for diagnosis, monitoring of therapy and drug delivery system. Many therapeutic agents are suggested to decrease NVs biogenesis.

Keywords: Drug delivery; Erythrocytes; Extracellular vesicles; Nanovesicles.

Figure 1

General mechanism of biogenesis and release of extracellular vesicles (EVs), MVs bud directly from the plasma membrane, whereas exosomes are formed by budding of early endosomes.

Figure 2

Proposed mechanism of oxidative stress induced erythrocyte vesiculation. EDNVs biogenesis triggered calcium concentrations that activate calpain, scramblase, and flippase.

Figure 3

Erythrocyte and erythrocyte derived nanovesicles (EDNV) as drug delivery systems and as stealth for nanoparticles. As drug delivery system erythrocyte is used for sustained release, targeting, bioreactor and biomimics stealth. However, EDNV is mainly used as targeting and EDNV stealth vehicle. Preswelling is performed using hypotonic NaCl solution, whereas resealing step is achieved using hypertonic NaCl solution.

Figure 4

Therapeutic interventions that modulate NVs biogenesis from erythrocytes.