Red Blood Cell Extracellular Vesicle-Based Drug Delivery: Challenges and Opportunities.

Wararat Chiangjong,Suradej Hongeng,Somchai Chutipongtanate,Pukkavadee Netsirisawan

doi:10.3389/fmed.2021.761362

Abstract

Recently, red blood cell-derived extracellular vesicles (RBCEVs) have attracted attention for clinical applications because of their safety and biocompatibility. RBCEVs can escape macrophages through the binding of CD47 to inhibitory receptor signal regulatory protein α. Furthermore, genetic materials such as siRNA, miRNA, mRNA, or single-stranded RNA can be encapsulated within RBCEVs and then released into target cells for precise treatment. However, their side effects, half-lives, target cell specificity, and limited large-scale production under good manufacturing practice remain challenging. In this review, we summarized the biogenesis and composition of RBCEVs, discussed the advantages and disadvantages of RBCEVs for drug delivery compared with synthetic nanovesicles and non-red blood cell-derived EVs, and provided perspectives for overcoming current limitations to the use of RBCEVs for clinical applications.

Highlights

Extracellular vesicles (EVs) are cell-derived vesicles present in bodily fluids that play an essential role in intercellular communication between tumor cells and other cells within the tumor micro- and macroenvironment [1]
These secreted membranous vesicles are currently separated into three main classes on the basis of their size and biogenesis as follows: (i) apoptotic bodies (800–5,000 nm in diameter) released by cells undergoing programmed cell death; (ii) microvesicles (MVs; 50–1,000 nm in diameter), which are large membranous vesicles produced via plasma membrane budding; and (iii) exosomes (40–100 nm in diameter), which are small vesicles originating from the endosomal compartment [2, 3]
This review focuses on red blood cell-derived extracellular vesicles (RBCEVs) as robust nanocarriers with potential utility in future strategies as drug delivery platforms for clinical applications

Summary

Introduction

Extracellular vesicles (EVs) are cell-derived vesicles present in bodily fluids that play an essential role in intercellular communication between tumor cells and other cells within the tumor micro- and macroenvironment [1]. EVs released from cells of the disease state contain specific molecules that could serve as biomarkers, and may function as the mediators/aggravators of pathophysiologic processes [8,9,10,11]. RBC-derived extracellular vesicles (RBCEVs) are generated in circulation via shedding of the plasma membrane caused by complement-mediated calcium influx, followed by vesicle shedding [13].

Results

Conclusion