Exosomes as nanobiological carriers of apotransferrin for therapeutic use in demyelinating diseases

PEREYRA GERBER, P; PASQUINI, JM; MATTERA, VANESA S; CORREALE, J; GLISONI, R

Montreal

Congreso; ISN-ASN 2019 Meeting; 2019

INTERNATIONAL SOCIETY FOR NEUROCHEMISTRY

Exosomes are extracellular vesicles with a diameter rangingbetween 20 and 100 nm and their capacity for biologic informationtransfer makes them an attractive tool as therapeutic agents fornanodelivery to specific target cells. In addition, their structure isbiocompatible, protecting the cargo from degradation. Also, thisvesicles are able to cross the blood brain barrier and increase cargomolecule stability, solubility and bioavailability. Previous studies inour laboratory demonstrated the pro-myelinating and differentiatingeffect of apoTransferrin (aTf) in the CNS. The present work focuseson the development of an aTf nanoencapsulation system to betargeted to oligodendroglial cells by intranasal administration incuprizone- demyelinated mice. Exosomes isolated from differentsources such as plasma, glial and neuronal cell lines and primarycultures were characterized by Western blot, scanning electronmicroscopy and dynamic light scattering to verify their purity,structural integrity and average size. Given that some exosomescontain the Tf receptor 1 (TfR1), our interest is to find an easy andquick pathway to load them with aTf and use them as a deliveryparticle of this growth factor to the target cells. Western blotanalyses of experiments conducted using exosomes isolated fromcell line OLN93 demonstrate that exosomes are able to be chargedwith aTf. Flow cytometry experiments showed that exosomesisolated from human plasma are able to bind exogenous aTf toTfR1. Altogether, our studies succeeded in thoroughly characterizing the isolated nanoparticles are exosomes and show that, due tothe presence of TfR1, these growth factor are able to bind aTf andfunction as nanocarriers of this protein in an animal demyelinationmodel.