Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells

Heikki Saari, Elisa Lázaro-Ibáñez, Tapani Viitala, Elina Vuorimaa-Laukkanen, Pia Siljander, Marjo Yliperttula

    Research output: Contribution to journalArticleScientificpeer-review

    512 Citations (Scopus)

    Abstract

    Background Extracellular vesicles (EVs) are naturally occurring membrane particles that mediate intercellular communication by delivering molecular information between cells. In this study, we investigated the effectiveness of two different populations of EVs (microvesicle- and exosome-enriched) as carriers of Paclitaxel to autologous prostate cancer cells. Methods EVs were isolated from LNCaP- and PC-3 prostate cancer cell cultures using differential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and Western blot. The uptake of microvesicles and exosomes by the autologous prostate cancer cells was assessed by flow cytometry and confocal microscopy. The EVs were loaded with Paclitaxel and the effectiveness of EV-mediated drug delivery was assessed with viability assays. The distribution of EVs and EV-delivered Paclitaxel in cells was inspected by confocal microscopy. Results Our main finding was that the loading of Paclitaxel to autologous prostate cancer cell-derived EVs increased its cytotoxic effect. This capacity was independent of the EV population and the cell line tested. Although the EVs without the drug increased cancer cell viability, the net effect of enhanced cytotoxicity remained. Both EV populations delivered Paclitaxel to the recipient cells through endocytosis, leading to the release of the drug from within the cells. The removal of EV surface proteins did not affect exosomes, while the drug delivery mediated by microvesicles was partially inhibited. Conclusions Cancer cell-derived EVs can be used as effective carriers of Paclitaxel to their parental cells, bringing the drug into the cells through an endocytic pathway and increasing its cytotoxicity. However, due to the increased cell viability, the use of cancer cell-derived EVs must be further investigated before any clinical applications can be designed.
    Original languageEnglish
    Pages (from-to)727-737
    Number of pages11
    JournalJournal of Controlled Release
    Volume220
    DOIs
    Publication statusPublished - 2015
    Publication typeA1 Journal article-refereed

    Keywords

    • Extracellular vesicles
    • Microvesicles
    • Exosomes
    • Paclitaxel
    • Drug delivery
    • Prostate cancer

    Publication forum classification

    • Publication forum level 3

    Fingerprint

    Dive into the research topics of 'Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells'. Together they form a unique fingerprint.

    Cite this