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Article

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

1
Department of Pharmacy, National University of Singapore, Singapore 117559, Singapore
2
Department of Surgery, National University of Singapore, Singapore 119228, Singapore
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Cardiovascular Research Institute, National University Heart Centre, Singapore 117599, Singapore
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NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119077, Singapore
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Antimicrobial Resistance Interdisciplinary Research Group (AMR-IRG), Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore
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School of Materials, Science and Engineering & Lee Kong Chian School of Medicine (LKC Medicine), Nanyang Technological University, Singapore 308232, Singapore
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Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CS Utrecht, The Netherlands
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Department of Targeted Therapeutics, University of Twente, 7522 NB Enschede, The Netherlands
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Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
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Department of Physiology, National University of Singapore, Singapore 117593, Singapore
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NUSNNI-NanoCore, National University of Singapore, Singapore 117574, Singapore
*
Authors to whom correspondence should be addressed.
Equal contribution.
Academic Editor: Carlotta Marianecci
Pharmaceutics 2021, 13(7), 1052; https://doi.org/10.3390/pharmaceutics13071052
Received: 3 June 2021 / Revised: 4 July 2021 / Accepted: 7 July 2021 / Published: 9 July 2021
(This article belongs to the Special Issue Development of Micro and Nano Systems for the Drug Delivery)
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. View Full-Text
Keywords: cell-derived nanovesicles; exosome mimetics; bionanotechnology; lyophilization; trehalose; cardioprotection cell-derived nanovesicles; exosome mimetics; bionanotechnology; lyophilization; trehalose; cardioprotection
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MDPI and ACS Style

Neupane, Y.R.; Huang, C.; Wang, X.; Chng, W.H.; Venkatesan, G.; Zharkova, O.; Wacker, M.G.; Czarny, B.; Storm, G.; Wang, J.-W.; Pastorin, G. Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles. Pharmaceutics 2021, 13, 1052. https://doi.org/10.3390/pharmaceutics13071052

AMA Style

Neupane YR, Huang C, Wang X, Chng WH, Venkatesan G, Zharkova O, Wacker MG, Czarny B, Storm G, Wang J-W, Pastorin G. Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles. Pharmaceutics. 2021; 13(7):1052. https://doi.org/10.3390/pharmaceutics13071052

Chicago/Turabian Style

Neupane, Yub Raj, Chenyuan Huang, Xiaoyuan Wang, Wei Heng Chng, Gopalakrishnan Venkatesan, Olga Zharkova, Matthias Gerhard Wacker, Bertrand Czarny, Gerrit Storm, Jiong-Wei Wang, and Giorgia Pastorin. 2021. "Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles" Pharmaceutics 13, no. 7: 1052. https://doi.org/10.3390/pharmaceutics13071052

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