FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel
Saari, H.; Lisitsyna, E.; Rautaniemi, K.; Rojalin, T.; Niemi, L.; Nivaro, O.; Laaksonen, T.; Yliperttula, M.; Vuorimaa-Laukkanen, E. (2018-08-28)
Saari, H.
Lisitsyna, E.
Rautaniemi, K.
Rojalin, T.
Niemi, L.
Nivaro, O.
Laaksonen, T.
Yliperttula, M.
Vuorimaa-Laukkanen, E.
28.08.2018
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tty-201807262022
https://urn.fi/URN:NBN:fi:tty-201807262022
Kuvaus
Peer reviewed
Tiivistelmä
In response to physiological and artificial stimuli, cells generate nano-scale extracellular vesicles (EVs) by encapsulating biomolecules in plasma membrane-derived phospholipid envelopes. These vesicles are released to bodily fluids, hence acting as powerful endogenous mediators in intercellular signaling. EVs provide a compelling alternative for biomarker discovery and targeted drug delivery, but their kinetics and dynamics while interacting with living cells are poorly understood. Here we introduce a novel method, fluorescence lifetime imaging microscopy (FLIM) to investigate these interaction attributes. By FLIM, we show distinct cellular uptake mechanisms of different EV subtypes, exosomes and microvesicles, loaded with anti-cancer agent, paclitaxel. We demonstrate differences in intracellular behavior and drug release profiles of paclitaxel-containing EVs. Exosomes seem to deliver the drug mostly by endocytosis while microvesicles enter the cells by both endocytosis and fusion with cell membrane. This research offers a new real-time method to investigate EV kinetics with living cells, and it is a potential advancement to complement the existing techniques. The findings of this study improve the current knowledge in exploiting EVs as next-generation targeted drug delivery systems.
Kokoelmat
- TUNICRIS-julkaisut [16929]