Red blood cell-derived extracellular vesicles as biomaterials: the opportunity of freezing-induced accelerated aging
Paolini L, Romano M, Mangolini V, Tassoni S, Jiang S, Mazzoldi EL, Musicò A, Zendrini A, Kashkanova A, Sandoghdar V, Berardi AC, Giliani SC, Bergese P, Radeghieri A (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 14
Pages Range: 122-139
Journal Issue: 1
DOI: 10.1039/d5bm01349f
Abstract
Red blood cell-derived extracellular vesicles (RBC-EVs) are emerging as promising biomaterials for next-generation drug delivery, owing to their intrinsic biocompatibility, immune-evasion properties, and minimal oncogenic risk. However, their broader application is currently limited by unresolved challenges related to heterogeneity, reproducibility, and long-term storage stability. By combining discontinuous sucrose density gradient separation with high-resolution interferometric nanoparticle tracking analysis, we identified a sharp bimodal size distribution of vesicles in freshly prepared samples. We then tracked how long-term storage at −80 °C drove their conversion into a monomodal distribution. To reproduce these conditions in a shorter time frame, we developed an “accelerated-ageing” protocol based on freeze–thaw cycles that generates RBC-EV samples with homogeneous density, size distribution, and biological activity, effectively replicating the properties of preparations stored for six months at −80 °C. This new vesicle population remains stable and retains membrane integrity and cellular internalization capacity, as confirmed by surface-associated enzymatic activity assays and uptake tests in cancer cell lines. These results suggest that freezing-induced “accelerated ageing” represents an effective method for the optimization and standardization of RBC-EVs as building blocks for biomaterial and bioengineering applications.
Authors with CRIS profile
Involved external institutions
Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light
Germany (DE)
Center for Colloid and Surface Science (CSGI)
Italy (IT)
Università degli Studi di Brescia
Italy (IT)
Germany (DE)
Center for Colloid and Surface Science (CSGI)
Italy (IT)
Università degli Studi di Brescia
Italy (IT)
How to cite
APA:
Paolini, L., Romano, M., Mangolini, V., Tassoni, S., Jiang, S., Mazzoldi, E.L.,... Radeghieri, A. (2026). Red blood cell-derived extracellular vesicles as biomaterials: the opportunity of freezing-induced accelerated aging. Biomaterials Science, 14(1), 122-139. https://doi.org/10.1039/d5bm01349f
MLA:
Paolini, Lucia, et al. "Red blood cell-derived extracellular vesicles as biomaterials: the opportunity of freezing-induced accelerated aging." Biomaterials Science 14.1 (2026): 122-139.
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