Author:
Holst Mikkel Roland,de Wit Nienke Marije,Ozgür Burak,Brachner Andreas,Hyldig Kathrine,Appelt-Menzel Antje,Sleven Hannah,Cader Zameel,de Vries Helga Eveline,Neuhaus Winfried,Jensen Allan,Brodin Birger,Nielsen Morten Schallburg
Abstract
AbstractHere, we report an experimental setup to benchmark different receptors for targeted therapeutic antibody delivery at the blood–brain barrier. We used brain capillary endothelial-like cells derived from induced pluripotent stem cells (hiPSC-BECs) as a model system and compared them to colon epithelial Caco-2 cells. This approach helped to identify favourable receptors for transport into the cell layer itself or for directing transport for transcytosis across the cell layer. The sorting receptors transferrin receptor and sortilin were shown to be efficient as antibody cargo receptors for intracellular delivery to the cell layer. In contrast, the cell surface receptors CD133 and podocalyxin were identified as static and inefficient receptors for delivering cargo antibodies. Similar to in vivo studies, the hiPSC-BECs maintained detectable transcytotic transport via transferrin receptor, while transcytosis was restricted using sortilin as a cargo receptor. Based on these findings, we propose the application of sortilin as a cargo receptor for delivering therapeutic antibodies into the brain microvascular endothelium.
Graphical Abstract
Funder
European Union’s Horizon 2020 research and innovation programme and EFPIA
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology,General Medicine
Cited by
1 articles.
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