Engineered EVs for Oxidative Stress Protection
Extracellular vesicles (EVs) are increasingly studied as vectors for drug delivery because they can transfer a variety of molecules across biological barriers. SerpinB3 is a serine protease inhibitor that has shown a protective anti-apoptotic function in a variety of stressful conditions. The aim of...
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doaj-7e84797b475a443e8b4f24d7cedbd8e02021-08-26T14:12:04ZengMDPI AGPharmaceuticals1424-82472021-07-011470370310.3390/ph14080703Engineered EVs for Oxidative Stress ProtectionAnna Maria Tolomeo0Santina Quarta1Alessandra Biasiolo2Mariagrazia Ruvoletto3Michela Pozzobon4Giada De Lazzari5Ricardo Malvicini6Cristian Turato7Giorgio Arrigoni8Patrizia Pontisso9Maurizio Muraca10Department of Women’s and Children’s Health, University of Padova, Via Giustiniani, 35128 Padova, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, Via Giustiniani, 35128 Padova, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, Via Giustiniani, 35128 Padova, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, Via Giustiniani, 35128 Padova, ItalyDepartment of Women’s and Children’s Health, University of Padova, Via Giustiniani, 35128 Padova, ItalyDepartment of Women’s and Children’s Health, University of Padova, Via Giustiniani, 35128 Padova, ItalyDepartment of Women’s and Children’s Health, University of Padova, Via Giustiniani, 35128 Padova, ItalyDepartment of Molecular Medicine, University of Pavia, 9 Via A Ferrata, 27100 Pavia, ItalyDepartment of Biomedical Sciences, University of Padova, 35121 Padova, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, Via Giustiniani, 35128 Padova, ItalyDepartment of Women’s and Children’s Health, University of Padova, Via Giustiniani, 35128 Padova, ItalyExtracellular vesicles (EVs) are increasingly studied as vectors for drug delivery because they can transfer a variety of molecules across biological barriers. SerpinB3 is a serine protease inhibitor that has shown a protective anti-apoptotic function in a variety of stressful conditions. The aim of this study was to evaluate protection from oxidative stress-induced damage, using extracellular vesicles that overexpress SerpinB3 (EVs-SB3) in order to enhance the effect of extracellular vesicles on cellular homeostasis. EVs-SB3s were obtained from HepG2 cells engineered to overexpress SerpinB3 and they revealed significant proteomic changes, mostly characterized by a reduced expression of other proteins compared with EVs from non-engineered cells. These EV preparations showed a significantly higher protection from H<sub>2</sub>O<sub>2</sub> induced oxidative stress in both the hepatoma cell line and in primary cardiomyocytes, compared to cells treated with naïve EVs or SerpinB3 alone, used at the same concentration. In conclusion, the induction of SerpinB3 transgene expression results in the secretion of EVs enriched with the protein product that exhibits enhanced cytoprotective activity, compared with naïve EVs or the nude SerpinB3 protein.https://www.mdpi.com/1424-8247/14/8/703extracellular vesiclesSerpinB3oxidative stresscytoprotection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Maria Tolomeo Santina Quarta Alessandra Biasiolo Mariagrazia Ruvoletto Michela Pozzobon Giada De Lazzari Ricardo Malvicini Cristian Turato Giorgio Arrigoni Patrizia Pontisso Maurizio Muraca |
spellingShingle |
Anna Maria Tolomeo Santina Quarta Alessandra Biasiolo Mariagrazia Ruvoletto Michela Pozzobon Giada De Lazzari Ricardo Malvicini Cristian Turato Giorgio Arrigoni Patrizia Pontisso Maurizio Muraca Engineered EVs for Oxidative Stress Protection Pharmaceuticals extracellular vesicles SerpinB3 oxidative stress cytoprotection |
author_facet |
Anna Maria Tolomeo Santina Quarta Alessandra Biasiolo Mariagrazia Ruvoletto Michela Pozzobon Giada De Lazzari Ricardo Malvicini Cristian Turato Giorgio Arrigoni Patrizia Pontisso Maurizio Muraca |
author_sort |
Anna Maria Tolomeo |
title |
Engineered EVs for Oxidative Stress Protection |
title_short |
Engineered EVs for Oxidative Stress Protection |
title_full |
Engineered EVs for Oxidative Stress Protection |
title_fullStr |
Engineered EVs for Oxidative Stress Protection |
title_full_unstemmed |
Engineered EVs for Oxidative Stress Protection |
title_sort |
engineered evs for oxidative stress protection |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2021-07-01 |
description |
Extracellular vesicles (EVs) are increasingly studied as vectors for drug delivery because they can transfer a variety of molecules across biological barriers. SerpinB3 is a serine protease inhibitor that has shown a protective anti-apoptotic function in a variety of stressful conditions. The aim of this study was to evaluate protection from oxidative stress-induced damage, using extracellular vesicles that overexpress SerpinB3 (EVs-SB3) in order to enhance the effect of extracellular vesicles on cellular homeostasis. EVs-SB3s were obtained from HepG2 cells engineered to overexpress SerpinB3 and they revealed significant proteomic changes, mostly characterized by a reduced expression of other proteins compared with EVs from non-engineered cells. These EV preparations showed a significantly higher protection from H<sub>2</sub>O<sub>2</sub> induced oxidative stress in both the hepatoma cell line and in primary cardiomyocytes, compared to cells treated with naïve EVs or SerpinB3 alone, used at the same concentration. In conclusion, the induction of SerpinB3 transgene expression results in the secretion of EVs enriched with the protein product that exhibits enhanced cytoprotective activity, compared with naïve EVs or the nude SerpinB3 protein. |
topic |
extracellular vesicles SerpinB3 oxidative stress cytoprotection |
url |
https://www.mdpi.com/1424-8247/14/8/703 |
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1721190871090593792 |