Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier
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Here, 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: [Figure not available: see fulltext.]
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 82 |
| Tidsskrift | Fluids and Barriers of the CNS |
| Vol/bind | 20 |
| Udgave nummer | 1 |
| Antal sider | 17 |
| ISSN | 2045-8118 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We are grateful to Mette Richner (Aarhus University) for creating the graphical abstract of this study. Annemette Boe Marnow and Diana Hudecz (Aarhus University) are thanked for their technical assistance. We thank Sabrina Oerter (Fraunhofer Institute for Silicate Research ISC) and Sanjana Mathew-Schmitt (University Hospital Würzburg) for kind technical advice and Mie Kristensen (Copenhagen University) for advice in Caco-2 culturing. We thank the generous funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 807015. JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Funding Information:
European Union’s Horizon 2020 research and innovation programme and EFPIA.
Funding Information:
This study was generous funded from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 807015. JU receives support from the.
Funding Information:
We are grateful to Mette Richner (Aarhus University) for creating the graphical abstract of this study. Annemette Boe Marnow and Diana Hudecz (Aarhus University) are thanked for their technical assistance. We thank Sabrina Oerter (Fraunhofer Institute for Silicate Research ISC) and Sanjana Mathew-Schmitt (University Hospital Würzburg) for kind technical advice and Mie Kristensen (Copenhagen University) for advice in Caco-2 culturing. We thank the generous funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 807015. JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Publisher Copyright:
© 2023, The Author(s).
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