Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin.

Autor: Mattera VS; CONICET. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires, Buenos Aires, Argentina., Pereyra Gerber P; Facultad de Farmacia y Bioquímica, Departamento de Química Biológica. Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina., Glisoni R; Facultad de Farmacia y Bioquímica, Departamento de Tecnología Farmacéutica, Universidad de Buenos Aires, Buenos Aires, Argentina.; Instituto de Nanobiotecnología (NANOBIOTEC), Universidad de Buenos Aires. CONICET, Buenos Aires, Argentina., Ostrowski M; Facultad de Farmacia y Bioquímica, Departamento de Química Biológica. Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina., Verstraeten SV; CONICET. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires, Buenos Aires, Argentina.; Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires. CONICET, Buenos Aires, Argentina., Pasquini JM; CONICET. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires, Buenos Aires, Argentina.; Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires. CONICET, Buenos Aires, Argentina., Correale JD; FLENI, Buenos Aires, Argentina.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2020 Nov; Vol. 155 (3), pp. 327-338. Date of Electronic Publication: 2020 Apr 28.
DOI: 10.1111/jnc.15019
Abstrakt: Previous work by our group has shown the pro-differentiating effects of apotransferrin (aTf) on oligodendroglial cells in vivo and in vitro. Further studies showed the remyelinating effect of aTf in animal demyelination models such as hypoxia/ischemia, where the intranasal administration of human aTf provided brain neuroprotection and reduced white matter damage, neuronal loss, and astrogliosis in different brain regions. These data led us to search for a less invasive and controlled technique to deliver aTf to the CNS. To such end, we isolated extracellular vesicles (EVs) from human and mouse plasma and different neuron and glia conditioned media and characterized them based on their quality, quantity, identity, and structural integrity by western blot, dynamic light scattering, and scanning electron microscopy. All sources yielded highly pure vesicles whose size and structures were in keeping with previous literary evidence. Given that, remarkably, EVs from all sources analyzed contained Tf receptor 1 (TfR1) in their composition, we employed two passive cargo-loading strategies which rendered successful EV loading with aTf, specifically through binding to TfR1. These results unveil EVs as potential nanovehicles of aTf to be delivered into the CNS parenchyma, and pave the way for further studies into their possible clinical application in the treatment of demyelinating diseases.
(© 2020 International Society for Neurochemistry.)
Databáze: MEDLINE
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