The future of Extracellular Vesicles as Theranostics – an ISEV meeting report

Soekmadji, Carolina; Li, Bo; Huang, Yiyao; Wang, Haifang; An, Tongqing; Liu, Chunchen; Pan, Weilun; Chen, Jing; Cheung, Lesley; Falcón‐Pérez, Juan Manuel; Gho, Yong Song; Holthöfer, Harry; Le, Minh Vuong; Marcilla, Antonio; O’Driscoll, Lorraine; Shekari, Faezeh; Shen, Tang‐Long; Torrecilhas, Ana Claúdia; Yan, Xiaomei; Yang, Fuquan; Yin, Hang; Xiao, Yu; Zhao, Zezhou; Zou, Xingxing; Wang, Qian; Zheng, Lei

doi:10.1080/20013078.2020.1809766

Cited by 97 publications

(109 citation statements)

References 106 publications

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“…injection, they were functionalized with PEG 18,38,45 . Although PEGylation of EVs reduced their uptake by B16.F10 cells compared to uncoated EVs (Figure 3) which has been previously shown in other studies 46 , the preferential uptake of PEG-functionalized EVs by 4-fold (Figure 3) compared to the uptake of PEG-coated liposomes highlighted their increased tumor cell specificity mediated by lipid and protein (eg, integrins, tetraspanins, glycoproteins) interactions which play a major role in EV intratumor biodistribution and uptake 47,48 .…”

Section: Discussionsupporting

confidence: 58%

“…To identify EV membrane proteins potentially involved in the preferential EV uptake as well as specific uptake by recipient cells, ToppGene and FunRich functional enrichment analysis highlighted that a majority of these proteins were associated with specific cellular uptake mediated by receptor or co-receptor activity delineating their importance for EV internalization via exogenous protein binding (Table 1, Figure 4C and D). Tetraspanins and integrins are ubiquitous surface molecules associated with EV uptake and exosome homing to specific tissues 10,48 . In MS data we identified several such proteins as for example the tetraspanins 3, -4, -6, -9, and -14, CD9, CD63, CD82, CD109, CD151, and the integrins β1, α -4, -5, -V, -6x1A, -9 (Supplementary file S1).…”

Section: Discussionmentioning

confidence: 99%

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Trojan Horse Treatment Based on Peg-Coated Extracellular Vesicles to Deliver Doxorubicin to Melanoma in Vitro and in Vivo

Li¹,

Ae²,

Cva³

et al. 2021

Preprint

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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). Nanosized 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 vitro and 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: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Trojan Horse Treatment Based on Peg-Coated Extracellular Vesicles to Deliver Doxorubicin to Melanoma in Vitro and in Vivo

Li¹,

Ae²,

Cva³

et al. 2021

Preprint

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“…uEV analysis can be focused on physical parameters (e.g., concentration, size distribution, morphology) and/or the biochemical content of uEVs (e.g., proteins, nucleic acids, lipids and metabolites). This is reflected by the wealth of state of the art and newly emerging EV assays and analysis technologies available (Hartjes et al., 2019; Nazarenko, 2020; Paisrisarn et al., 2020; Skotland et al., 2020; Soekmadji et al., 2020; Williams et al., 2019).…”

Section: Recommendations and Considerationsmentioning

confidence: 99%

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

Erdbrügger

Blijdorp

Bijnsdorp

et al. 2021

J of Extracellular Vesicle

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233

273

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“…Thus, studies characterizing EV glycosylation profiles of healthy individuals and cancer patients resorting to high-resolution methods are a need to identify potential novel cancer biomarkers. As an important remark, the standardization of current EV isolation/characterization protocols across the world remains a milestone to uniformize and ensure the reproducibility of studies conducted in the field, especially those aiming to be translated into the clinical setting [ 222 ].…”

Section: Discussionmentioning

confidence: 99%

Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications

Martins

Ramos

Freitas

et al. 2021

Cells

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Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.

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The future of Extracellular Vesicles as Theranostics – an ISEV meeting report

Cited by 97 publications

References 106 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

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications

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