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

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskningpeer 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.
OriginalsprogDansk
TitelFinal Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark
ForlagUniversity of Copenhagen
Publikationsdato2016
Sider51
ArtikelnummerP-51
StatusUdgivet - 2016
Begivenhed19th International Symposium on Signal Transduction at the Blood-Brain Barriers - København, Danmark
Varighed: 14 sep. 201616 sep. 2016

Konference

Konference19th International Symposium on Signal Transduction at the Blood-Brain Barriers
Land/OmrådeDanmark
ByKøbenhavn
Periode14/09/201616/09/2016

Citationsformater