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

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.

Extracellular Vesicle-Based Method for Detecting MYCN Amplification Status of Pediatric Neuroblastoma

“…EVs are lipid bilayer-encapsulated nanoparticles released from all cells and present in all kinds of biofluids. EVs are known to play crucial roles in cell-to-cell communication and physiological regulation in both healthy and disease states, some of which have therapeutic potential [ 16 , 17 , 18 , 19 ]. EVs contain molecular signatures of original cells including lipids, proteins and nucleic acids, and thus serve as a promising source for biomarker discovery [ 15 , 16 ].…”

“…EVs contain molecular signatures of original cells including lipids, proteins and nucleic acids, and thus serve as a promising source for biomarker discovery [ 15 , 16 ]. EVs can be classified into three subtypes based on their biogenesis pathways and bio-physico-chemical properties [ 18 , 19 , 20 ]. Exosomes (Exo) are the small EVs (40–150 nm in diameter), which originate from the endosomal pathway and multivesicular bodies, and are enriched with common exosome markers, e.g., Alix, Tsg101, Hsp70 and tetraspanins [ 18 , 19 , 20 ].…”

“…EVs can be classified into three subtypes based on their biogenesis pathways and bio-physico-chemical properties [ 18 , 19 , 20 ]. Exosomes (Exo) are the small EVs (40–150 nm in diameter), which originate from the endosomal pathway and multivesicular bodies, and are enriched with common exosome markers, e.g., Alix, Tsg101, Hsp70 and tetraspanins [ 18 , 19 , 20 ]. Microvesicles (MVs) are the large EVs (150–1000 nm in diameter) produced from plasma membrane budding and thus share the membrane and cytosolic proteins of parent cells [ 18 , 19 , 20 ].…”

“…Exosomes (Exo) are the small EVs (40–150 nm in diameter), which originate from the endosomal pathway and multivesicular bodies, and are enriched with common exosome markers, e.g., Alix, Tsg101, Hsp70 and tetraspanins [ 18 , 19 , 20 ]. Microvesicles (MVs) are the large EVs (150–1000 nm in diameter) produced from plasma membrane budding and thus share the membrane and cytosolic proteins of parent cells [ 18 , 19 , 20 ]. Apoptotic-derived EVs or apoptotic bodies (>1000 nm in diameter) are generated from plasma membrane blebbing during cell apoptosis [ 18 , 19 , 20 ].…”

“…Microvesicles (MVs) are the large EVs (150–1000 nm in diameter) produced from plasma membrane budding and thus share the membrane and cytosolic proteins of parent cells [ 18 , 19 , 20 ]. Apoptotic-derived EVs or apoptotic bodies (>1000 nm in diameter) are generated from plasma membrane blebbing during cell apoptosis [ 18 , 19 , 20 ]. Exo and MVs are the main focus of the EV-based method development for several cancers, i.e., head and neck [ 16 ], brain [ 21 ], lung [ 22 ], colon [ 23 ], bladder [ 24 ], endometrial [ 25 ], ovarian [ 26 ] and prostate [ 27 ].…”