Monitoring cell endocytosis of liposomes by real-time electrical impedance spectroscopy

Claudia Caviglia, Francesca Garbarino, Chiara Canali, Fredrik Melander, Roberto Raiteri, Giorgio Ferrari, Marco Sampietro, Arto Heiskanen, Thomas Lars Andresen, Kinga Zor*, Jenny Emnéus

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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. Real-time 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. [Figure not available: see fulltext.]
Original languageEnglish
JournalAnalytical and Bioanalytical Chemistry
Volume412
Issue number24
Pages (from-to)6371-6380
Number of pages10
ISSN1618-2642
DOIs
Publication statusPublished - 2020

Keywords

  • Real-time monitoring
  • Electrical impedance spectroscopy
  • Cell morphology
  • Matrix metalloproteinase
  • Cytotoxicity
  • Liposome endocytosis

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