Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle-Mimetic Nanovesicles Loaded with Chemotherapeutics

Sergey Brezgin; Anastasiya Kostyusheva; Natalia Ponomareva; Ekaterina Bayurova; Anastasia Frolova; Olga Slatinskaya; Landysh Fatkhutdinova; Georgy Maksimov; Mikhail Zyuzin; Ilya Gordeychuk; Sergey Makarov; Alexander V. Ivanov; Andrey Zamyatnin; Vladimir Chulanov; Alessandro Parodi; Dmitry Kostyushev

doi:10.20944/preprints202212.0060.v1

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preprints.org > chemistry and materials science > nanotechnology > doi: 10.20944/preprints202212.0060.v1

Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle-Mimetic Nanovesicles Loaded with Chemotherapeutics

Sergey Brezgin

Anastasiya Kostyusheva

Landysh Fatkhutdinova

^* ,

Version 1 : Received: 4 December 2022 / Approved: 5 December 2022 / Online: 5 December 2022 (06:04:21 CET)

A peer-reviewed article of this Preprint also exists.

Brezgin, S.; Kostyusheva, A.; Ponomareva, N.; Bayurova, E.; Kondrashova, A.; Frolova, A.; Slatinskaya, O.; Fatkhutdinova, L.; Maksimov, G.; Zyuzin, M.; Gordeychuk, I.; Lukashev, A.; Makarov, S.; Ivanov, A.; Zamyatnin, A.A., Jr.; Chulanov, V.; Parodi, A.; Kostyushev, D. Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle–Mimetic Nanovesicles Loaded with Chemotherapeutics. Pharmaceutics 2023, 15, 534. Brezgin, S.; Kostyusheva, A.; Ponomareva, N.; Bayurova, E.; Kondrashova, A.; Frolova, A.; Slatinskaya, O.; Fatkhutdinova, L.; Maksimov, G.; Zyuzin, M.; Gordeychuk, I.; Lukashev, A.; Makarov, S.; Ivanov, A.; Zamyatnin, A.A., Jr.; Chulanov, V.; Parodi, A.; Kostyushev, D. Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle–Mimetic Nanovesicles Loaded with Chemotherapeutics. Pharmaceutics 2023, 15, 534.

Abstract

Because of their high biocompatibility, stability, ability to negotiate biological barrier passage, and functionalization properties, biological nanoparticles have been actively investigated for many medical applications. Biological nanoparticles, including natural extracellular vesicles (EVs) and synthetic extracellular vesicle-mimetic nanovesicles (EMNVs) represent novel drug delivery vehicles that can accommodate different payloads. In this study, we investigated EVs and EMNVs for their physical, biological and delivery properties and we showed that EMNVs have similar delivery properties compared to EVs. In addition, these nanotherapeutics were analyzed for their cytostatic properties in combination with the FDA-approved drug hydroxychloroquine (HCQ), which increased their cytostatic thanks to its lysosome-destabilizing properties. Altogether, these data demonstrated that, at least in vitro, the use of synthetic biomimetic particles is comparable to the natural counterparts, while their synthesis is significantly faster and more cost effective. In addition, we highlighted the benefits of combining biological nanoparticles with a lysosome destabilizing agent that increased the delivery properties of the particles.

Keywords

exosomes; extrusion; proteolipid nanoparticles; drug delivery; nanomedicine; doxorubicin; ex-truded nanoparticles; hydroxychloroquine; endolysosomal escape; lysosomotropic

Subject

Chemistry and Materials Science, Nanotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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