A post-insertion strategy for surface functionalization of bacterial and mammalian cell-derived extracellular vesicles

Jiang, Linglei; Ulsen, Peter van; Kooijmans, Sander A.A.; Kessel, Kok P. M. van; Jong, Wouter S. P.; Essen, Max van; Seinen, Cor; Maat, Steven de; Jong, Olivier G. de; Gitz-François, Jerney F.F.; Hennink, Wim E.; Vader, Pieter; Schiffelers, Raymond M.

doi:10.1016/j.bbagen.2020.129763

Cited by 16 publications

(12 citation statements)

References 11 publications

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“… 18 From this standpoint, we used the post-micellar insertion technique to directly engineer these EVs with DSPE-PEG 2000 moieties that could confer them increased circulation longevity to an extent that, as far as current studies can confirm, minimally affects their structural properties, composition, and does not majorly interfere with their uptake by target cells. 18 , 47 , 48 Thus, we show that although PEGylation of EVs significantly reduced their uptake by B16.F10 cells compared to uncoated EVs ( Figure 3 ) which is consistent with other studies, 18 , 49 the preferential uptake of PEG-functionalized EVs by fourfold ( Figure 3 ) compared to the uptake of PEG-coated liposomes demonstrates their increased tumor cell specificity and uptake mediated by lipid and protein (e.g., integrins, tetraspanins, and glycoproteins) interactions, which may likely play a major role in EV intratumor biodistribution and uptake in vivo . 50 , 51 …”

Section: Discussionmentioning

confidence: 99%

Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo

Pătraș

Ionescu

Munteanu

et al. 2021

Cancer Biology & Therapy

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Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX). Small EVs were efficiently enriched from melanoma cells cultured under metabolic stress by ultrafiltration coupled with size exclusion chromatography (UF-SEC) and characterized by size, morphology, and proteome. To reduce their clearance in vivo , EVs were PEGylated and passively loaded with DOX (PEG-EV-DOX). Our data suggested that the low PEG coverage of EVs might still favor EV surface protein interactions with target proteins from intratumor cells, ensuring their use as “Trojan horses” to deliver DOX to the tumor tissue. Moreover, our results showed a superior antitumor activity of PEG-EV-DOX in B16.F10 murine melanoma models in vivo compared to that exerted by clinically applied liposomal DOX in the same tumor model. The PEG-EV-DOX administration in vivo reduced NF-κB activation and increased BAX expression, suggesting better prognosis of EV-based therapy than liposomal DOX treatment. Collectively, our results highlight the promising potential of EVs as optimal tools for systemic delivery of DOX to solid tumors.

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Section: Discussionmentioning

confidence: 99%

Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo

Pătraș

Ionescu

Munteanu

et al. 2021

Cancer Biology & Therapy

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“…Alternatively, another new vaccination method that is actively being explored involves the use of cell-derived bi-layered extracellular vesicles (EVs) such as exosomes, microvesicles and apoptotic bodies [ 156 , 157 ]. Indeed, these have great advantages in terms of delivery and can increase overall immunogenicity since they have immunostimulatory molecules on their surfaces such as MHC class I or II molecules [ 156 , 158 ]. Further, exosomes have the capacity to carry pathogen antigens, as was shown by Montaner-Tarbes et al in a study analyzing exosomes from pigs infected with porcine reproductive and respiratory virus (PRRSV) [ 159 ].…”

Section: Discussionmentioning

confidence: 99%

AMDV Vaccine: Challenges and Perspectives

Markarian

Abrahamyan

2021

Viruses

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Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control the viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control the viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by the immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease.

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“…Alternatively, another new vaccination method that is actively being explored involves the use of cell-derived bi-layered extracellular vesicles (EVs) such as exosomes, microvesicles and apoptotic bodies [162,163]. Indeed, these have great advantages in terms of delivery and can increase overall immunogenicity since they have immunostimulatory molecules on their surfaces such as MHC class I or II molecules [162,164]. Further, exosomes have the capacity to carry pathogen antigens, as was shown by Montaner-Tarbes et al in a study analyzing exosomes from pigs infected with porcine reproductive and respiratory virus (PRRSV) [165].…”

Section: Discussionmentioning

confidence: 99%

AMDV Vaccine: Challenges and Perspectives

Markarian

Abrahamyan

2021

Preprint

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Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease.

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A post-insertion strategy for surface functionalization of bacterial and mammalian cell-derived extracellular vesicles

Cited by 16 publications

References 11 publications

Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo

Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo

AMDV Vaccine: Challenges and Perspectives

AMDV Vaccine: Challenges and Perspectives

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