02291nas a2200289   4500000000100000008004100001260001500042653002700057653003200084653002300116653002600139653005100165100002300216700002600239700002900265700001900294700002100313700001900334700001700353700001600370245014100386856004700527300000800574490000700582520139800589022001401987       2023                            d  c2023-03-2910aAlzheimer disease (AD)10aBlood–brain barrier (BBB)10aGold nanoparticles10aorgan-on-a-chip (OoC)10aTrans-endothelial electrical resistance (TEER)1 aSujey Palma-Florez1 aAdrián López-Canosa1 aFrancisco Moralez-Zavala1 aOscar Castaño1 aMarcelo J. Kogan1 aJosep Samitier1 aAnna Lagunas1 aMònica Mir00aBBB-on-a-chip with integrated micro-TEER for permeability evaluation of multi-functionalized gold nanorods against Alzheimer’s disease  uhttps://doi.org/10.1186/s12951-023-01798-2  a1150 v213 aThe lack of predictive models that mimic the blood–brain barrier (BBB) hinders the development of effective drugs for neurodegenerative diseases. Animal models behave differently from humans, are expensive and have ethical constraints. Organ-on-a-chip (OoC) platforms offer several advantages to resembling physiological and pathological conditions in a versatile, reproducible, and animal-free manner. In addition, OoC give us the possibility to incorporate sensors to determine cell culture features such as trans-endothelial electrical resistance (TEER). Here, we developed a BBB-on-a-chip (BBB-oC) platform with a TEER measurement system in close distance to the barrier used for the first time for the evaluation of the permeability performance of targeted gold nanorods for theranostics of Alzheimer’s disease. GNR-PEG-Ang2/D1 is a therapeutic nanosystem previously developed by us consisting of gold nanorods (GNR) functionalized with polyethylene glycol (PEG), angiopep-2 peptide (Ang2) to overcome the BBB and the D1 peptide as beta amyloid fibrillation inhibitor, finally obtaining GNR-PEG-Ang2/D1 which showed to be useful for disaggregation of the amyloid in in vitro and in vivo models. In this work, we evaluated its cytotoxicity, permeability, and some indications of its impact on the brain endothelium by employing an animal-free device based on neurovascular human cells.  a1477-3155