TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - https://doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - https://doi.org/10.3109/03602532.2012.738687 SN - 1097-9883 IS - 1 SP - 110 EP - 121 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Henderson, Colin J. A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man JF - Expert Review of Clinical Pharmacology Y1 - 2009 U6 - https://doi.org/10.1586/17512433.2.2.105 SN - 1751-2441 VL - 2 IS - 2 SP - 105 EP - 109 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior JF - Drug Metabolism Reviews Y1 - 2009 U6 - https://doi.org/10.1080/03602530802605040 SN - 1097-9883 VL - 41 IS - 1 SP - 27 EP - 65 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity JF - Drug Metabolism Reviews Y1 - 2006 U6 - https://doi.org/10.1080/03602530600786232 SN - 1097-9883 VL - 38 IS - 3 SP - 515 EP - 597 ER - TY - JOUR A1 - Dadfar, Dryed Mohammadali A1 - Camozzi, Denise A1 - Darguzyte, Milita A1 - Roemhild, Karolin A1 - Varvarà, Paola A1 - Metselaar, Josbert A1 - Banala, Srinivas A1 - Straub, Marcel A1 - Güver, Nihan A1 - Engelmann, Ulrich M. A1 - Slabu, Ioana A1 - Buhl, Miriam A1 - Leusen, Jan van A1 - Kögerler, Paul A1 - Hermanns-Sachweh, Benita A1 - Schulz, Volkmar A1 - Kiessling, Fabian A1 - Lammers, Twan T1 - Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance JF - Journal of Nanobiotechnology N2 - Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications. Y1 - 2020 U6 - https://doi.org/10.1186/s12951-020-0580-1 SN - 1477-3155 VL - 18 IS - Article number 22 SP - 1 EP - 13 PB - Nature Portfolio ER - TY - JOUR A1 - Slabu, Ioana A1 - Roeth, Anjali A. A1 - Engelmann, Ulrich M. A1 - Wiekhorst, Frank A1 - Buhl, Eva M. A1 - Neumann, Ulf P. A1 - Schmitz-Rode, Thomas T1 - Modeling of magnetoliposome uptake in human pancreatic tumor cells in vitro JF - Nanotechnology Y1 - 2019 U6 - https://doi.org/10.1088/1361-6528/ab033e SN - 1361-6528 VL - 30 IS - 18 SP - 184004 ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Shasha, Carolyn A1 - Teeman, Eric A1 - Slabu, Iona A1 - Krishnan, Kannan M. T1 - Predicting size-dependent heating efficiency of magnetic nanoparticles from experiment and stochastic Néel-Brown Langevin simulation JF - Journal of Magnetism and Magnetic Materials Y1 - 2019 U6 - https://doi.org/10.1016/j.jmmm.2018.09.041 SN - 0304-8853 VL - 471 IS - 1 SP - 450 EP - 456 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Seifert, Julian A1 - Mues, Benedikt A1 - Roitsch, Stefan A1 - Ménager, Christine A1 - Schmidt, Annette M. A1 - Slabu, Ioana T1 - Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels JF - Journal of Magnetism and Magnetic Materials Y1 - 2019 U6 - https://doi.org/10.1016/j.jmmm.2018.09.113 SN - 0304-8853 VL - 471 IS - 1 SP - 486 EP - 494 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Roeth, Anjali A.J. A1 - Eberbeck, Dietmar A1 - Buhl, Eva Miriam A1 - Neumann, Ulf Peter A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells JF - Scientific Reports N2 - Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-31553-9 SN - 2045-2322 VL - 8 IS - 1 SP - Article number 13210 PB - Springer Nature CY - Cham ER -