Monitoring cell endocytosis of liposomes by real-time electrical impedance spectroscopy
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RESEARCH PAPER
Monitoring cell endocytosis of liposomes by real-time electrical impedance spectroscopy Claudia Caviglia 1,2 & Francesca Garbarino 1 & Chiara Canali 1,3 & Fredrik Melander 1,4 & Roberto Raiteri 5 & Giorgio Ferrari 6 & Marco Sampietro 6 & Arto Heiskanen 1,7 & Thomas Lars Andresen 1,4 & Kinga Zór 1,8 & Jenny Emnéus 1,7 Received: 15 December 2019 / Revised: 4 March 2020 / Accepted: 9 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Evaluation and understanding the effect of drug delivery in in vitro systems is fundamental in drug discovery. We present an assay based on real-time electrical impedance spectroscopy (EIS) measurements that can be used to follow the internalisation and cytotoxic effect of a matrix metalloproteinase (MMP)–sensitive liposome formulation loaded with oxaliplatin (OxPt) on colorectal cancer cells. The EIS response identified two different cellular processes: (i) a negative peak in the cell index (CI) within the first 5 h, due to onset of liposome endocytosis, followed by (ii) a subsequent CI increase, due to the reattachment of cells until the onset of cytotoxicity with a decrease in CI. Free OxPt or OxPt-loaded Stealth liposomes did not show this two-stage EIS response; the latter can be due to the fact that Stealth cannot be cleaved by MMPs and thus is not taken up by the cells. Realtime bright-field imaging supported the EIS data, showing variations in cell adherence and cell morphology after exposure to the different liposome formulations. A drastic decrease in cell coverage as well as rounding up of cells during the first 5 h of exposure to OxPt-loaded (MMP)-sensitive liposome formulation is reflected by the first negative EIS response, which indicates the onset of liposome endocytosis. Keywords Real-time monitoring . Electrical impedance spectroscopy . Cell morphology . Matrix metalloproteinase . Cytotoxicity . Liposome endocytosis Published in the topical collection featuring Female Role Models in Analytical Chemistry. Francesca Garbarino and Chiara Canali contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00216-020-02592-x) contains supplementary material, which is available to authorized users. * Claudia Caviglia [email protected]
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Present address: Department of Health Technology, Technical University of Denmark, Produktionstorvet, Building 423, 2800 Kongens Lyngby, Denmark
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Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genova, Via All’Opera Pia, 11A, 16145 Genoa, Italy
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Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet, Building 423, 2800 Kongens Lyngby, Denmark
Department of Electronics, Information and Bioengineering, Polytechnic University of Milan, P.za Leonardo da Vinci, 32, 20133 Milan, Italy
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Present address: Radiometer Medical ApS, Åkandevej 21, 2700 Brønshøj, Denmark
Present address: Department of Biotechnology and Biomedicine, Technical Univer
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