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

Heikki Saari, Elisa Lazaro Ibanez, Tapani Viitala, Elina Vuorimaa-Laukkanen, Pia Siljander, Marjo Yliperttula

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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. (C) 2015 The Authors. Published by Elsevier B.V.
Alkuperäiskielienglanti
LehtiJournal of Controlled Release
Vuosikerta220
Sivut727-737
Sivumäärä11
ISSN0168-3659
DOI - pysyväislinkit
TilaJulkaistu - 24 syyskuuta 2015
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 317 Farmasia
  • 1182 Biokemia, solu- ja molekyylibiologia

Lainaa tätä

@article{e76346511db642e0af143745eb0f3b40,
title = "Microvesicle- and exosome- mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells",
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. (C) 2015 The Authors. Published by Elsevier B.V.",
keywords = "317 Pharmacy, Extracellular vesicles, Microvesicles, Exosomes, Paclitaxel, Drug delivery, Prostate cancer, TUMOR-GROWTH, BRAIN, 1182 Biochemistry, cell and molecular biology",
author = "Heikki Saari and {Lazaro Ibanez}, Elisa and Tapani Viitala and Elina Vuorimaa-Laukkanen and Pia Siljander and Marjo Yliperttula",
year = "2015",
month = "9",
day = "24",
doi = "10.1016/j.jconrel.2015.09.031",
language = "English",
volume = "220",
pages = "727--737",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier Scientific Publ. Co",

}

Microvesicle- and exosome- mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. / Saari, Heikki ; Lazaro Ibanez, Elisa; Viitala, Tapani ; Vuorimaa-Laukkanen, Elina; Siljander, Pia ; Yliperttula, Marjo .

julkaisussa: Journal of Controlled Release, Vuosikerta 220, 24.09.2015, s. 727-737.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Microvesicle- and exosome- mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells

AU - Saari, Heikki

AU - Lazaro Ibanez, Elisa

AU - Viitala, Tapani

AU - Vuorimaa-Laukkanen, Elina

AU - Siljander, Pia

AU - Yliperttula, Marjo

PY - 2015/9/24

Y1 - 2015/9/24

N2 - 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. (C) 2015 The Authors. Published by Elsevier B.V.

AB - 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. (C) 2015 The Authors. Published by Elsevier B.V.

KW - 317 Pharmacy

KW - Extracellular vesicles

KW - Microvesicles

KW - Exosomes

KW - Paclitaxel

KW - Drug delivery

KW - Prostate cancer

KW - TUMOR-GROWTH

KW - BRAIN

KW - 1182 Biochemistry, cell and molecular biology

UR - http://www.sciencedirect.com/science/article/pii/S0168365915301322

U2 - 10.1016/j.jconrel.2015.09.031

DO - 10.1016/j.jconrel.2015.09.031

M3 - Article

VL - 220

SP - 727

EP - 737

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -