Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier

Kasper Bendix Johnsen, Annette Burkhart Larsen, Jonas Bruun, Piotr Siupka, Morten Schallburg Nielsen, Thomas Lars Andresen, Torben Moos

Research output: Contribution to book/anthology/report/conference proceedingConference abstract in proceedingResearchpeer-review

Abstract

Brain capillary endothelial cells (BCECs) express
transferrin receptors as opposed to endothelial cells of
any organ in the remaining body, suggesting that targeting
to the transferrin receptors as a reasonable strategy for
delivering drugs to the CNS. However, as the
intracellular trafficking of transferrin receptor does not
suggest transcytosis through BCECs of ligands and
antibodies bound to the receptor, another strategy for
transport through the BBB is to target nanocarriers, e.g.
liposomes, to BCEC, which may allow the carriers to
release their content within the BCECs with a subsequent
transport further into the CNS.
We studied transferrin receptor-targeted (OX26)
immunoliposomes containing oxaliplatin with the aim of
quantifying the uptake of OX26, liposomes and oxaliplatin
in BCECs and the remaining CNS. The uptake of the
immunoliposomes and their cargo was studied in 18-dayold
rats in which the expression of transferrin receptors
by BCECs is almost twice as high as in the adult rat. For
mechanistic purposes additional uptake studies were
performed in primary rat BBB cultures consisting of
BCECs and astrocytes.
The uptake of OX26-conjugated immunoliposomes
by BCECs were significantly higher both in vitro
and in vivo when compared to isotypic IgG-conjugated
liposomes. Quantitative analyses after capillary depletion
revealed cargo transport from BCECs to the remaining
CNS, but not differences could be detected between OX26-
conjugated and isotype IgG control liposomes in vivo,
whereas isotype IgG control liposomes were superior in
vitro. In conclusion, OX26-targeted immunoliposomes are
suitable for uptake by BCECs, which may be exploited for
controlled release of a drug compound within the BCEC.
Original languageDanish
Title of host publicationFinal Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark
PublisherUniversity of Copenhagen
Publication date2016
Pages51
Article numberP-51
Publication statusPublished - 2016
Event19th International Symposium on Signal Transduction at the Blood-Brain Barriers - København, Denmark
Duration: 14 Sep 201616 Sep 2016

Conference

Conference19th International Symposium on Signal Transduction at the Blood-Brain Barriers
CountryDenmark
CityKøbenhavn
Period14/09/201616/09/2016

Cite this

Johnsen, K. B., Larsen, A. B., Bruun, J., Siupka, P., Nielsen, M. S., Andresen, T. L., & Moos, T. (2016). Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier. In Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark (pp. 51). [P-51] University of Copenhagen.
Johnsen, Kasper Bendix ; Larsen, Annette Burkhart ; Bruun, Jonas ; Siupka, Piotr ; Nielsen, Morten Schallburg ; Andresen, Thomas Lars ; Moos, Torben. / Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier. Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark. University of Copenhagen, 2016. pp. 51
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title = "Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier",
abstract = "Brain capillary endothelial cells (BCECs) expresstransferrin receptors as opposed to endothelial cells ofany organ in the remaining body, suggesting that targetingto the transferrin receptors as a reasonable strategy fordelivering drugs to the CNS. However, as theintracellular trafficking of transferrin receptor does notsuggest transcytosis through BCECs of ligands andantibodies bound to the receptor, another strategy fortransport through the BBB is to target nanocarriers, e.g.liposomes, to BCEC, which may allow the carriers torelease their content within the BCECs with a subsequenttransport further into the CNS.We studied transferrin receptor-targeted (OX26)immunoliposomes containing oxaliplatin with the aim ofquantifying the uptake of OX26, liposomes and oxaliplatinin BCECs and the remaining CNS. The uptake of theimmunoliposomes and their cargo was studied in 18-dayoldrats in which the expression of transferrin receptorsby BCECs is almost twice as high as in the adult rat. Formechanistic purposes additional uptake studies wereperformed in primary rat BBB cultures consisting ofBCECs and astrocytes.The uptake of OX26-conjugated immunoliposomesby BCECs were significantly higher both in vitroand in vivo when compared to isotypic IgG-conjugatedliposomes. Quantitative analyses after capillary depletionrevealed cargo transport from BCECs to the remainingCNS, but not differences could be detected between OX26-conjugated and isotype IgG control liposomes in vivo,whereas isotype IgG control liposomes were superior invitro. In conclusion, OX26-targeted immunoliposomes aresuitable for uptake by BCECs, which may be exploited forcontrolled release of a drug compound within the BCEC.",
author = "Johnsen, {Kasper Bendix} and Larsen, {Annette Burkhart} and Jonas Bruun and Piotr Siupka and Nielsen, {Morten Schallburg} and Andresen, {Thomas Lars} and Torben Moos",
year = "2016",
language = "Dansk",
pages = "51",
booktitle = "Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark",
publisher = "University of Copenhagen",

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Johnsen, KB, Larsen, AB, Bruun, J, Siupka, P, Nielsen, MS, Andresen, TL & Moos, T 2016, Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier. in Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark., P-51, University of Copenhagen, pp. 51, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, København, Denmark, 14/09/2016.

Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier. / Johnsen, Kasper Bendix; Larsen, Annette Burkhart; Bruun, Jonas; Siupka, Piotr; Nielsen, Morten Schallburg; Andresen, Thomas Lars; Moos, Torben.

Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark. University of Copenhagen, 2016. p. 51 P-51.

Research output: Contribution to book/anthology/report/conference proceedingConference abstract in proceedingResearchpeer-review

TY - ABST

T1 - Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier

AU - Johnsen, Kasper Bendix

AU - Larsen, Annette Burkhart

AU - Bruun, Jonas

AU - Siupka, Piotr

AU - Nielsen, Morten Schallburg

AU - Andresen, Thomas Lars

AU - Moos, Torben

PY - 2016

Y1 - 2016

N2 - Brain capillary endothelial cells (BCECs) expresstransferrin receptors as opposed to endothelial cells ofany organ in the remaining body, suggesting that targetingto the transferrin receptors as a reasonable strategy fordelivering drugs to the CNS. However, as theintracellular trafficking of transferrin receptor does notsuggest transcytosis through BCECs of ligands andantibodies bound to the receptor, another strategy fortransport through the BBB is to target nanocarriers, e.g.liposomes, to BCEC, which may allow the carriers torelease their content within the BCECs with a subsequenttransport further into the CNS.We studied transferrin receptor-targeted (OX26)immunoliposomes containing oxaliplatin with the aim ofquantifying the uptake of OX26, liposomes and oxaliplatinin BCECs and the remaining CNS. The uptake of theimmunoliposomes and their cargo was studied in 18-dayoldrats in which the expression of transferrin receptorsby BCECs is almost twice as high as in the adult rat. Formechanistic purposes additional uptake studies wereperformed in primary rat BBB cultures consisting ofBCECs and astrocytes.The uptake of OX26-conjugated immunoliposomesby BCECs were significantly higher both in vitroand in vivo when compared to isotypic IgG-conjugatedliposomes. Quantitative analyses after capillary depletionrevealed cargo transport from BCECs to the remainingCNS, but not differences could be detected between OX26-conjugated and isotype IgG control liposomes in vivo,whereas isotype IgG control liposomes were superior invitro. In conclusion, OX26-targeted immunoliposomes aresuitable for uptake by BCECs, which may be exploited forcontrolled release of a drug compound within the BCEC.

AB - Brain capillary endothelial cells (BCECs) expresstransferrin receptors as opposed to endothelial cells ofany organ in the remaining body, suggesting that targetingto the transferrin receptors as a reasonable strategy fordelivering drugs to the CNS. However, as theintracellular trafficking of transferrin receptor does notsuggest transcytosis through BCECs of ligands andantibodies bound to the receptor, another strategy fortransport through the BBB is to target nanocarriers, e.g.liposomes, to BCEC, which may allow the carriers torelease their content within the BCECs with a subsequenttransport further into the CNS.We studied transferrin receptor-targeted (OX26)immunoliposomes containing oxaliplatin with the aim ofquantifying the uptake of OX26, liposomes and oxaliplatinin BCECs and the remaining CNS. The uptake of theimmunoliposomes and their cargo was studied in 18-dayoldrats in which the expression of transferrin receptorsby BCECs is almost twice as high as in the adult rat. Formechanistic purposes additional uptake studies wereperformed in primary rat BBB cultures consisting ofBCECs and astrocytes.The uptake of OX26-conjugated immunoliposomesby BCECs were significantly higher both in vitroand in vivo when compared to isotypic IgG-conjugatedliposomes. Quantitative analyses after capillary depletionrevealed cargo transport from BCECs to the remainingCNS, but not differences could be detected between OX26-conjugated and isotype IgG control liposomes in vivo,whereas isotype IgG control liposomes were superior invitro. In conclusion, OX26-targeted immunoliposomes aresuitable for uptake by BCECs, which may be exploited forcontrolled release of a drug compound within the BCEC.

M3 - Konferenceabstrakt i proceeding

SP - 51

BT - Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark

PB - University of Copenhagen

ER -

Johnsen KB, Larsen AB, Bruun J, Siupka P, Nielsen MS, Andresen TL et al. Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier. In Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark. University of Copenhagen. 2016. p. 51. P-51