Holst, Mikkel RolandMikkel RolandHolstWit, Nienke Marije deNienke Marije deWitOzgür, BurakBurakOzgürBrachner, AndreasAndreasBrachnerHyldig, KathrineKathrineHyldigAppelt-Menzel, AntjeAntjeAppelt-MenzelSleven, HannahHannahSlevenCader, ZameelZameelCaderVries, Helga Eveline deHelga Eveline deVriesNeuhaus, WinfriedWinfriedNeuhausJensen, AllanAllanJensenBrodin, BirgerBirgerBrodinSchallburg Nielsen, MortenMortenSchallburg Nielsen2023-11-222023-11-222023-12https://publica.fraunhofer.de/handle/publica/45715810.1186/s12987-023-00480-xHere, 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.enBlood-brain barrierBrain endothelial cellsCaco-2Cargo receptorCD133PodocalyxinReceptor-mediated transcytosisSortilinTherapeutic antibodiesTranscytosisTransferrin receptorDDC::600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheitjournal article