Abstract
Extracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. The dHL-60 cells are also easily loaded with various cargoes such as antibiotics (penicillin), anticancer drug (paclitaxel), chemoattractant (MCP-1), miRNA, and Cas9. The EVs derived from the dHL-60 cells showed efficient incorporation of these cargoes and significant effector functions, such as bactericidal activity, monocyte chemotaxis, and macrophage polarization. Our results suggest that neutrophils or neutrophil-like promyelocytic cells could be an attractive source for drug-delivery EVs.
Highlights
Extracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications
We found that the HL-60 and differentiated HL-60 (dHL-60) cells generated EVs in response to external stimulation
The cargoes-loaded EVs derived from the dHL-60 cells showed higher effector functions than those from the HL-60 cells
Summary
Extracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. These neutrophil-like differentiated HL-60 (dHL-60) cells have neutrophil characteristics, such as reactive oxygen species (ROS) generation, neutrophil extracellular trap (NET) formation, chemotaxis, and bactericidal a ctivity[17,18,19,20] They have a short-life span due to spontaneous apoptosis[21] which is an advantage over the EVs generated from general cancer cells. Recent studies employed dHL-60 cells to investigate NDEVs22,23 and found the beneficial effects on inflammatory diseases, such as acute lung injury and s troke[22,23]
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