Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs

Claudia Caviglia, Kinga Zor, Lucia Montini, Valeria Tilli, Silvia Canepa, Fredrik Melander, Layla Bashir Larsen, Marco Carminati, Giorgio Ferrari, Roberto Raiteri, Arto Heiskanen, Thomas Lars Andresen, Jenny Emnéus

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    Abstract

    In this work, we have developed a microfluidic cytotoxicity assay for a cell culture and detection platform, which enables both fluid handling and electrochemical/optical detection. The cytotoxic effect of anticancer drugs doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes, developed for targeted drug delivery, was evaluated using real-time impedance monitoring. The time-dependent effect of DOX on HeLa cells was monitored and found to have a delayed onset of cytotoxicity in microfluidics compared with static culture conditions based on data obtained in our previous study. The result of a fluorescent microscopic annexin V/propidium iodide assay, performed in microfluidics, confirmed the outcome of the real-time impedance assay. In addition, the response of HeLa cells to OX-induced cytotoxicity proved to be slower than toxicity induced by DOX. A difference in the time-dependent cytotoxic response of fibrosarcoma cells (HT1080) to free OX and OX-loaded liposomes was observed and attributed to incomplete degradation of the liposomes, which results in lower drug availability. The matrix metalloproteinase (MMP)-dependent release of OX from OX-loaded liposomes was also confirmed using laryngopharynx carcinoma cells (FaDu). The comparison and the observed differences between the cytotoxic effects under microfluidic and static conditions highlight the importance of comparative studies as basis for implementation of microfluidic cytotoxic assays.
    Original languageEnglish
    JournalAnalytical chemistry
    Volume87
    Issue number4
    Pages (from-to)2204-2212
    Number of pages9
    ISSN0003-2700
    DOIs
    Publication statusPublished - 2015

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