title: Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs.
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.
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark , DK-2800 Kongens Lyngby, Denmark.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caviglia
authors.forename: Kinga
authors.initials: K
authors.lastname: Zór
authors.forename: Lucia
authors.initials: L
authors.lastname: Montini
authors.forename: Valeria
authors.initials: V
authors.lastname: Tilli
authors.forename: Silvia
authors.initials: S
authors.lastname: Canepa
authors.forename: Fredrik
authors.initials: F
authors.lastname: Melander
authors.forename: Haseena B
authors.initials: HB
authors.lastname: Muhammad
authors.forename: Marco
authors.initials: M
authors.lastname: Carminati
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ferrari
authors.forename: Roberto
authors.initials: R
authors.lastname: Raiteri
authors.forename: Arto
authors.initials: A
authors.lastname: Heiskanen
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andresen
authors.forename: Jenny
authors.initials: J
authors.lastname: Emnéus
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D004317:Doxorubicin