FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel

H. Saari, E. Lisitsyna, K. Rautaniemi, T. Rojalin, L. Niemi, O. Nivaro, T. Laaksonen, M. Yliperttula, E. Vuorimaa-Laukkanen

    Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

    18 Sitaatiot (Scopus)
    37 Lataukset (Pure)

    Abstrakti

    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.

    AlkuperäiskieliEnglanti
    Sivut133-143
    Sivumäärä11
    JulkaisuJournal of Controlled Release
    Vuosikerta284
    DOI - pysyväislinkit
    TilaJulkaistu - 28 elok. 2018
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

    Julkaisufoorumi-taso

    • Jufo-taso 3

    !!ASJC Scopus subject areas

    • Pharmaceutical Science

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