# name
Study of the transport of substances across the blood-brain barrier with the 8D3 anti-transferrin receptor antibody

# metadata.dc.description[].value
Podeu consultar el llibre complet a: http://hdl.handle.net/2445/128014

# metadata.dc.description.abstract[].value
Numerous strategies have been proposed to overcome the blood-brain barrier (BBB) and efficiently deliver therapeutic agents to the brain. One of these strategies consists of linking the pharmacologically active substance to a molecular vector that acts as a molecular Trojan Horse and is capable of crossing the BBB using a receptor-mediated transcellular transport system of the brain capillary endothelial cells (BCECs). The transferrin receptor (TfR) is related to a transcytosis process in these cells, and the 8D3 monoclonal antibody (mAb), directed against the mouse TfR, is able to induce a receptor response. Thus, the 8D3 antibody could be a potential molecular Trojan Horse to transport pharmacologically active substances across the BBB. On these bases, a series of experiments were performed where the 8D3 antibody was conjugated to different cargoes, the resulting constructs were administered in vivo to mice, and the distribution and intracellular mechanisms that these constructs undergo at the BBB were
studied. Our results indicated a TfR-mediated and clathrin-dependent internalization
process by which the 8D3-cargo constructs enters the BCEC. The resulting endocytic
vesicles follow at least two different routes. On one hand, most vesicles enter intracellular
processes of vesicular fusion and rearrangement in which the cargo is guided to late
endosomes, multivesicular bodies or lysosomes. On the other hand, a small but not
negligible percentage of the vesicles follow a different route in which they fuse with the
abluminal membrane and open towards the basal lamina, indicating a potential route for
the delivery of therapeutic substances. In this route, however, the 8D3−cargo remain fixed
to the abluminal membrane, indicating that the 8D3 is maintained linked to the TfR, and
the cargo does not go beyond the basal membrane. Altogether, different optimization
approaches need to be developed for efficient drug delivery, but receptor-mediated
transport (RMT) continues to be one of the most promising strategies to overcome the
BBB.

# metadata.dc.relation.ispartof[].value
Recent Advances in Pharmaceutical Sciences VIII, 2018, Research Signpost. Editors: Diego Muñoz-Torrero, Yolanda Cajal and Joan Maria Llobet. ISBN: 978-81-308-0579-5. Chapter 4, p. 59-78

# metadata.dc.source[].value
Llibres / Capítols de llibre (Farmacologia, Toxicologia i Química Terapèutica)

# metadata.dc.title[].value
Study of the transport of substances across the blood-brain barrier with the 8D3 anti-transferrin receptor antibody