Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery

The main advantage of extracellular vesicles (EVs) as a drug carrier system is their low immunogenicity and internalization by mammalian cells. EVs are often considered a cell-specific delivery system, but the production of preparative amounts of EVs for therapeutic applications is challenging due t...

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Autores principales:	Anastasiya Oshchepkova, Oleg Markov, Evgeniy Evtushenko, Alexander Chernonosov, Elena Kiseleva, Ksenia Morozova, Vera Matveeva, Lyudmila Artemyeva, Valentin Vlassov, Marina Zenkova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	extracellular vesicles vesicle mimetic nucleic acid delivery cytochalasin B mesenchymal stem cells dendritic cells Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/6899df8448ab485598534bb14ee0641e
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spelling	oai:doaj.org-article:6899df8448ab485598534bb14ee0641e2021-11-25T18:41:44ZTropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery10.3390/pharmaceutics131119111999-4923https://doaj.org/article/6899df8448ab485598534bb14ee0641e2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1911https://doaj.org/toc/1999-4923The main advantage of extracellular vesicles (EVs) as a drug carrier system is their low immunogenicity and internalization by mammalian cells. EVs are often considered a cell-specific delivery system, but the production of preparative amounts of EVs for therapeutic applications is challenging due to their laborious isolation and purification procedures. Alternatively, mimetic vesicles prepared from the cellular plasma membrane can be used in the same way as natural EVs. For example, a cytoskeleton-destabilizing agent, such as cytochalasin B, allows the preparation of membrane vesicles by a series of centrifugations. Here, we prepared cytochalasin-B-inducible nanovesicles (CINVs) of various cellular origins and studied their tropism in different mammalian cells. We observed that CINVs derived from human endometrial mesenchymal stem cells exhibited an enhanced affinity to epithelial cancer cells compared to myeloid, lymphoid or neuroblastoma cancer cells. The dendritic cell-derived CINVs were taken up by all studied cell lines with a similar efficiency that differed from the behavior of DC-derived EVs. The ability of cancer cells to internalize CINVs was mainly determined by the properties of recipient cells, and the cellular origin of CINVs was less important. In addition, receptor-mediated interactions were shown to be necessary for the efficient uptake of CINVs. We found that CINVs, derived from late apoptotic/necrotic cells (aCINVs) are internalized by in myelogenous (K562) 10-fold more efficiently than CINVs, and interact much less efficiently with melanocytic (B16) or epithelial (KB-3-1) cancer cells. Finally, we found that CINVs caused a temporal and reversible drop of the rate of cell division, which restored to the level of control cells with a 24 h delay.Anastasiya OshchepkovaOleg MarkovEvgeniy EvtushenkoAlexander ChernonosovElena KiselevaKsenia MorozovaVera MatveevaLyudmila ArtemyevaValentin VlassovMarina ZenkovaMDPI AGarticleextracellular vesiclesvesicle mimeticnucleic acid deliverycytochalasin Bmesenchymal stem cellsdendritic cellsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1911, p 1911 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular vesicles vesicle mimetic nucleic acid delivery cytochalasin B mesenchymal stem cells dendritic cells Pharmacy and materia medica RS1-441
spellingShingle	extracellular vesicles vesicle mimetic nucleic acid delivery cytochalasin B mesenchymal stem cells dendritic cells Pharmacy and materia medica RS1-441 Anastasiya Oshchepkova Oleg Markov Evgeniy Evtushenko Alexander Chernonosov Elena Kiseleva Ksenia Morozova Vera Matveeva Lyudmila Artemyeva Valentin Vlassov Marina Zenkova Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery
description	The main advantage of extracellular vesicles (EVs) as a drug carrier system is their low immunogenicity and internalization by mammalian cells. EVs are often considered a cell-specific delivery system, but the production of preparative amounts of EVs for therapeutic applications is challenging due to their laborious isolation and purification procedures. Alternatively, mimetic vesicles prepared from the cellular plasma membrane can be used in the same way as natural EVs. For example, a cytoskeleton-destabilizing agent, such as cytochalasin B, allows the preparation of membrane vesicles by a series of centrifugations. Here, we prepared cytochalasin-B-inducible nanovesicles (CINVs) of various cellular origins and studied their tropism in different mammalian cells. We observed that CINVs derived from human endometrial mesenchymal stem cells exhibited an enhanced affinity to epithelial cancer cells compared to myeloid, lymphoid or neuroblastoma cancer cells. The dendritic cell-derived CINVs were taken up by all studied cell lines with a similar efficiency that differed from the behavior of DC-derived EVs. The ability of cancer cells to internalize CINVs was mainly determined by the properties of recipient cells, and the cellular origin of CINVs was less important. In addition, receptor-mediated interactions were shown to be necessary for the efficient uptake of CINVs. We found that CINVs, derived from late apoptotic/necrotic cells (aCINVs) are internalized by in myelogenous (K562) 10-fold more efficiently than CINVs, and interact much less efficiently with melanocytic (B16) or epithelial (KB-3-1) cancer cells. Finally, we found that CINVs caused a temporal and reversible drop of the rate of cell division, which restored to the level of control cells with a 24 h delay.
format	article
author	Anastasiya Oshchepkova Oleg Markov Evgeniy Evtushenko Alexander Chernonosov Elena Kiseleva Ksenia Morozova Vera Matveeva Lyudmila Artemyeva Valentin Vlassov Marina Zenkova
author_facet	Anastasiya Oshchepkova Oleg Markov Evgeniy Evtushenko Alexander Chernonosov Elena Kiseleva Ksenia Morozova Vera Matveeva Lyudmila Artemyeva Valentin Vlassov Marina Zenkova
author_sort	Anastasiya Oshchepkova
title	Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery
title_short	Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery
title_full	Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery
title_fullStr	Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery
title_full_unstemmed	Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery
title_sort	tropism of extracellular vesicles and cell-derived nanovesicles to normal and cancer cells: new perspectives in tumor-targeted nucleic acid delivery
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6899df8448ab485598534bb14ee0641e
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Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery

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