TY - JOUR
T1 - Study of the transcytosis of an anti-transferrin receptor antibody with a Fab′ cargo across the blood-brain barrier in mice
AU - Manich, Gemma
AU - Cabezón, Itsaso
AU - Del Valle, Jaume
AU - Duran-Vilaregut, Joaquim
AU - Camins, Antoni
AU - Pallàs, Mercè
AU - Pelegrí, Carme
AU - Vilaplana, Jordi
N1 - Funding Information:
This work was supported by the Ministerio de Ciencia e Innovación (Grants BFU/2009-08352 and BFU/2010-22149 ) and by the ‘ Generalitat de Catalunya ’ ( 2009/SGR853 ). This work is also included in the Nano-trans-brain project (CIBER-BBN) . The authors thank M. Calvo, from the Servei de Microscòpia Òptica Avançada of the Universitat de Barcelona, for her help in the FRET studies.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - One strategy used to transport pharmacologically active substances across the blood-brain barrier (BBB) is to link the substance to a molecule capable of crossing the BBB using a receptor-mediated transcellular transport system in brain capillary endothelial cells. The transferrin receptor (TfR) is related to a transcytosis process in these cells, and the 8D3 antibody, directed against mouse TfR, is able to induce a receptor response. In this work, the potential of 8D3 to carry molecules across the BBB was investigated. This antibody (either unlabeled or FITC-labeled) was intravenously administered to ICR-CD1 mice. Immunocomplexes (ICs) consisting of 8D3 antibody (carrier) and Fab′ fragments (simulated cargo), in some cases directly fluorolabeled with FITC, were also administered to ICR-CD1 mice. At different time-points of recirculation, the IC components were studied using immunohistochemical procedures and fluorescence resonance energy transfer (FRET). The results suggested that 8D3 alone or in an IC with Fab′ fragments entered the endothelial cells. FRET analysis indicated that the colocalization of their fluorescent signals inside the endothelial cells decreased with time, indicating that ICs can be processed and Fab′ fragments probably separated from 8D3. However, neither 8D3 alone nor the IC components crossed the BBB.
AB - One strategy used to transport pharmacologically active substances across the blood-brain barrier (BBB) is to link the substance to a molecule capable of crossing the BBB using a receptor-mediated transcellular transport system in brain capillary endothelial cells. The transferrin receptor (TfR) is related to a transcytosis process in these cells, and the 8D3 antibody, directed against mouse TfR, is able to induce a receptor response. In this work, the potential of 8D3 to carry molecules across the BBB was investigated. This antibody (either unlabeled or FITC-labeled) was intravenously administered to ICR-CD1 mice. Immunocomplexes (ICs) consisting of 8D3 antibody (carrier) and Fab′ fragments (simulated cargo), in some cases directly fluorolabeled with FITC, were also administered to ICR-CD1 mice. At different time-points of recirculation, the IC components were studied using immunohistochemical procedures and fluorescence resonance energy transfer (FRET). The results suggested that 8D3 alone or in an IC with Fab′ fragments entered the endothelial cells. FRET analysis indicated that the colocalization of their fluorescent signals inside the endothelial cells decreased with time, indicating that ICs can be processed and Fab′ fragments probably separated from 8D3. However, neither 8D3 alone nor the IC components crossed the BBB.
KW - 8D3 antibody
KW - Blood-brain barrier
KW - Receptor-mediated transcytosis
KW - Transferrin receptor
UR - http://www.scopus.com/inward/record.url?scp=84879488826&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2013.05.027
DO - 10.1016/j.ejps.2013.05.027
M3 - Artículo
AN - SCOPUS:84879488826
VL - 49
SP - 556
EP - 564
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
IS - 4
ER -