title: Europium complexes as novel indicators of paracellular diffusion.
abstract: Measurement of paracellular permeation is an important assay for tight-junction investigations of drug toxicity, especially for metal-based drugs, and routine validation of the integrity of cell monolayers for models of drug absorption. Great efforts have been made in discovery and validation of novel paracellular diffusion indicators. In the present work, we prepared three Eu complexes, i.e., [Eu(dtpa)] (dtpa=diethylenetriaminepentaacetic acid), [Eu(dtpa)(BSA)], and [Eu(dtpa)(PLL)] (PLL=poly(L-lysine)), and tested their permeation properties on Madin-Darby canine kidney (MDCK) cells. The experimental results showed that all three probes were nontoxic to MDCK cells, permeated across MDCK monolayer exclusively via the paracellular pathways, and responded well to the changes on tight junction with high correlation of P(app) values to the decrease of trans-epithelial electric resistance (TEER). In addition, time-resolved fluorescence assays were conducted in a high-sensitivity and background-free mode. All these results confirmed the Eu complexes as novel and practical paracellular indicators.
authors.affiliation: State Key Laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Xu
authors.forename: Chengyue
authors.initials: C
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004285:Dogs; D017097:Electric Impedance; D005063:Europium / Q000737:chemistry*; D061985:Madin Darby Canine Kidney Cells
chemical_list: D056831:Coordination Complexes; D005063:Europium