Cargando…

Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles

Recently, bioinspired cell-derived nanovesicles (CDNs) have gained much interest in the field of nanomedicine due to the preservation of biomolecular structure characteristics derived from their parent cells, which impart CDNs with unique properties in terms of binding and uptake by target cells and...

Descripción completa

Detalles Bibliográficos
Autores principales: Neupane, Yub Raj, Huang, Chenyuan, Wang, Xiaoyuan, Chng, Wei Heng, Venkatesan, Gopalakrishnan, Zharkova, Olga, Wacker, Matthias Gerhard, Czarny, Bertrand, Storm, Gerrit, Wang, Jiong-Wei, Pastorin, Giorgia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309024/
https://www.ncbi.nlm.nih.gov/pubmed/34371743
http://dx.doi.org/10.3390/pharmaceutics13071052
_version_ 1783728423507591168
author Neupane, Yub Raj
Huang, Chenyuan
Wang, Xiaoyuan
Chng, Wei Heng
Venkatesan, Gopalakrishnan
Zharkova, Olga
Wacker, Matthias Gerhard
Czarny, Bertrand
Storm, Gerrit
Wang, Jiong-Wei
Pastorin, Giorgia
author_facet Neupane, Yub Raj
Huang, Chenyuan
Wang, Xiaoyuan
Chng, Wei Heng
Venkatesan, Gopalakrishnan
Zharkova, Olga
Wacker, Matthias Gerhard
Czarny, Bertrand
Storm, Gerrit
Wang, Jiong-Wei
Pastorin, Giorgia
author_sort Neupane, Yub Raj
collection PubMed
description Recently, bioinspired cell-derived nanovesicles (CDNs) have gained much interest in the field of nanomedicine due to the preservation of biomolecular structure characteristics derived from their parent cells, which impart CDNs with unique properties in terms of binding and uptake by target cells and intrinsic biological activities. Although the production of CDNs can be easily and reproducibly achieved with any kind of cell culture, application of CDNs for therapeutic purposes has been greatly hampered by their physical and chemical instability during long-term storage in aqueous dispersion. In the present study, we conceived a lyophilization approach that would preserve critical characteristics regarding stability (vesicles’ size and protein content), structural integrity, and biological activity of CDNs for enabling long-term storage in freeze-dried form. Compared to the lyoprotectant sucrose, trehalose-lyoprotected CDNs showed significantly higher glass transition temperature and lower residual moisture content. As assessed by ATR-FTIR and far-UV circular dichroism, lyophilization in the presence of the lyoprotectant effectively maintained the secondary structure of cellular proteins. After reconstitution, lyoprotected CDNs were efficiently associated with HeLa cells, CT26 cells, and bone marrow-derived macrophages at a rate comparable to the freshly prepared CDNs. In vivo, both lyoprotected and freshly prepared CDNs, for the first time ever reported, targeted the injured heart, and exerted intrinsic cardioprotective effects within 24 h, attributable to the antioxidant capacity of CDNs in a myocardial ischemia/reperfusion injury animal model. Taken together, these results pave the way for further development of CDNs as cell-based therapeutics stabilized by lyophilization that enabled long-term storage while preserving their activity.
format Online
Article
Text
id pubmed-8309024
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83090242021-07-25 Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles Neupane, Yub Raj Huang, Chenyuan Wang, Xiaoyuan Chng, Wei Heng Venkatesan, Gopalakrishnan Zharkova, Olga Wacker, Matthias Gerhard Czarny, Bertrand Storm, Gerrit Wang, Jiong-Wei Pastorin, Giorgia Pharmaceutics Article Recently, bioinspired cell-derived nanovesicles (CDNs) have gained much interest in the field of nanomedicine due to the preservation of biomolecular structure characteristics derived from their parent cells, which impart CDNs with unique properties in terms of binding and uptake by target cells and intrinsic biological activities. Although the production of CDNs can be easily and reproducibly achieved with any kind of cell culture, application of CDNs for therapeutic purposes has been greatly hampered by their physical and chemical instability during long-term storage in aqueous dispersion. In the present study, we conceived a lyophilization approach that would preserve critical characteristics regarding stability (vesicles’ size and protein content), structural integrity, and biological activity of CDNs for enabling long-term storage in freeze-dried form. Compared to the lyoprotectant sucrose, trehalose-lyoprotected CDNs showed significantly higher glass transition temperature and lower residual moisture content. As assessed by ATR-FTIR and far-UV circular dichroism, lyophilization in the presence of the lyoprotectant effectively maintained the secondary structure of cellular proteins. After reconstitution, lyoprotected CDNs were efficiently associated with HeLa cells, CT26 cells, and bone marrow-derived macrophages at a rate comparable to the freshly prepared CDNs. In vivo, both lyoprotected and freshly prepared CDNs, for the first time ever reported, targeted the injured heart, and exerted intrinsic cardioprotective effects within 24 h, attributable to the antioxidant capacity of CDNs in a myocardial ischemia/reperfusion injury animal model. Taken together, these results pave the way for further development of CDNs as cell-based therapeutics stabilized by lyophilization that enabled long-term storage while preserving their activity. MDPI 2021-07-09 /pmc/articles/PMC8309024/ /pubmed/34371743 http://dx.doi.org/10.3390/pharmaceutics13071052 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Neupane, Yub Raj
Huang, Chenyuan
Wang, Xiaoyuan
Chng, Wei Heng
Venkatesan, Gopalakrishnan
Zharkova, Olga
Wacker, Matthias Gerhard
Czarny, Bertrand
Storm, Gerrit
Wang, Jiong-Wei
Pastorin, Giorgia
Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles
title Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles
title_full Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles
title_fullStr Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles
title_full_unstemmed Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles
title_short Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles
title_sort lyophilization preserves the intrinsic cardioprotective activity of bioinspired cell-derived nanovesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309024/
https://www.ncbi.nlm.nih.gov/pubmed/34371743
http://dx.doi.org/10.3390/pharmaceutics13071052
work_keys_str_mv AT neupaneyubraj lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT huangchenyuan lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT wangxiaoyuan lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT chngweiheng lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT venkatesangopalakrishnan lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT zharkovaolga lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT wackermatthiasgerhard lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT czarnybertrand lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT stormgerrit lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT wangjiongwei lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles
AT pastoringiorgia lyophilizationpreservestheintrinsiccardioprotectiveactivityofbioinspiredcellderivednanovesicles