Targeting Inflammatory Vasculature by Extracellular Vesicles

Wang, Sihan; Dong, Xinyue; Gao, Jin; Wang, Zhenjia

doi:10.1208/s12248-018-0200-2

Cited by 22 publications

(15 citation statements)

References 63 publications

(64 reference statements)

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“…These nanovesicles are similar to naturally secreted EVs but contain fewer subcellular organelles and nucleic acids. These EVs were loaded with the anti-inflammatory drug piceatannol and dramatically alleviated acute lung inflammation and sepsis induced by lipopolysaccharide [ 161 , 162 ]. Resolvin D2 was also loaded in PMN-EVs to enhance resolution of inflammation in a mouse stroke model system, therefore protecting the brain from damage during ischemic stroke [ 163 ].…”

Section: Neutrophil-derived Evsmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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Similar to other cell types, neutrophilic granulocytes also release extracellular vesicles (EVs), mainly medium-sized microvesicles/microparticles. According to published data, authors have reached a consensus on the physical parameters (size, density) and chemical composition (surface proteins, proteomics) of neutrophil-derived EVs. In contrast, there is large diversity and even controversy in the reported functional properties. Part of the discrepancy may be ascribed to differences in the viability of the starting cells, in eliciting factors, in separation techniques and in storage conditions. However, the most recent data from our laboratory prove that the same population of neutrophils is able to generate EVs with different functional properties, transmitting pro-inflammatory or anti-inflammatory effects on neighboring cells. Previously we have shown that Mac-1 integrin is a key factor that switches anti-inflammatory EV generation into pro-inflammatory and antibacterial EV production. This paper reviews current knowledge on the functional alterations initiated by neutrophil-derived EVs, listing their effects according to the triggering agents and target cells. We summarize the presence of neutrophil-derived EVs in pathological processes and their perspectives in diagnostics and therapy. Finally, the functional heterogeneity of differently triggered EVs indicates that neutrophils are capable of producing a broad spectrum of EVs, depending on the environmental conditions prevailing at the time of EV genesis.

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Section: Neutrophil-derived Evsmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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“…We recently reported an approach to generate double-layer membrane-derived nanovesicles (DMVs) from bacteria using nitrogen cavitation, and showed that DMVs can be used as a vaccine to combat bacterial infections 35 . Compared to OMVs 36 , DMVs constitute the whole membrane of gram-negative bacteria and contain endogenous cellular targeting ligands, and DMVs are also stable 26 , 35 , 37 . Our nitrogen cavitation method can be used to generate DMVs from any bacteria and is ready to scale up for translation of our technology 27 , 35 .…”

Section: Introductionmentioning

confidence: 99%

RGD-expressed bacterial membrane-derived nanovesicles enhance cancer therapy via multiple tumorous targeting

Gao¹,

Wang²,

Dong³

et al. 2021

Theranostics

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Background: A tumor microenvironment is a complicated multicellular system comprised of tumor cells, immune cells and blood vessels. Blood vessels are the barriers for drug tissue penetration. Effectively treating a cancer requires drug delivery systems to overcome biological barriers present in tumor microenvironments (TMEs). Methods: We designed a drug delivery system made of bacterial ( Escherichia coli ) double layer membrane-derived nanovesicles (DMVs) with the expression of RGD peptides and endogenous targeting ligands of bacteria. The physical and biological characteristics of DMVs were assessed by cryogenic transmission electron microscopy, western blotting, flow cytometry and confocal microscopy. Doxorubicin (DOX) was loaded in DMVs via a pH gradient driven drug loading method. Therapeutical effects of DOX-loaded DMVs were studied in a melanoma xenograft mouse model. Results: In vitro and in vivo experiments showed that DMVs can target neutrophils and monocytes that mediated the transport of DMVs across blood vessel barriers and they can also directly target tumor vasculature and tumor cells, resulting in enhanced delivery of therapeutics to TMEs. Furthermore, we developed a remote drug loading approach to efficiently encapsulate DOX inside DMVs, and the drug loading was 12% (w/w). In the B16-F10 melanoma mouse model, we showed that DOX-RGD-DMVs significantly inhibited the tumor growth compared to several controls. Conclusion: Our studies reveal that DMVs are a powerful tool to simultaneously target multiple cells in TMEs, thus increasing drug delivery for improved cancer therapies.

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“…Moreover, they have a short-life span due to spontaneous apoptosis 21 which is an advantage over the EVs generated from general cancer cells. Therefore, recent studies employed dHL-60 cells to investigate NDEVs 22 , 23 and found the beneficial effects on inflammatory diseases, such as acute lung injury and stroke 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Youn

Lee

et al. 2021

Sci Rep

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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.

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Targeting Inflammatory Vasculature by Extracellular Vesicles

Cited by 22 publications

References 63 publications

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

RGD-expressed bacterial membrane-derived nanovesicles enhance cancer therapy via multiple tumorous targeting

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

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