Extracellular vesicles from dHL-60 cells as delivery vehicles for diverse therapeutics

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.

Cell-derived extracellular vesicles for CRISPR/Cas9 delivery: engineering strategies for cargo packaging and loading

“…The recipient cells showed the highest GFP fluorescence. 40 This indicated that the EVs produced from dHL-60 cells could be a potential source for CRISPR/Cas9 RNP delivery. Besides, various engineering technologies have been developed to increase loading efficiency.…”

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

“…Dendritic cells (DCs), Mϕ, and neutrophils, including neutrophil-like promyelocytic cells, are increasingly recognized for their contributory roles in this context. DC-derived EVs, pivotal in the orchestration of immune responses, also partake in antigen presentation, a function that might be exploitable for disease-modifying strategies in NDDs [137][138][139]. Of particular interest are EVs from immature DCs, which are proficient in the release of EVs devoid of T-cell costimulatory molecules, such as major histocompatibility complex class II (MHC-II), thereby proffering an immunologically quiescent profile for therapeutic purposes [140].…”

“…Monocytes and Mϕ represent another cadre of cellular factories, capable of generating EVs that can elude the reticuloendothelial system, thereby circumventing one of the major barriers to effective drug delivery [138]. Such an attribute not only enhances the direct transport of therapeutic cargoes to targeted cells but also augments the therapeutic index of encapsulated drugs [139].…”

Extracellular vesicles: a rising star for therapeutics and drug delivery

“…The dHL-60 cell-derived EVs had higher effector functions (larger amounts and higher efficiencies), higher efficiency of EVs production, and lower immunogenicity than HL-60-derived EVs and neutrophil-derived extracellular vesicles (NDEVs). This suggests that neutrophils and neutrophillike promyelocytic cells could serve as a platform for EVs drug-loading [112]. Qiu et al developed an MSC-derived exosome (MSC-EXO) vector to deliver the cabazitaxel/ tumor necrosis factor-related apoptosis-inducing ligand (CTX/TRAIL) combination via transfection and achieved excellent antitumor activity.…”