Статья

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

H SaariDivision of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5E, 00014 Helsinki, FinlandElisa Lázaro‐IbáñezDivision of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5E, 00014 Helsinki, FinlandTapani ViitalaDivision of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5E, 00014 Helsinki, FinlandElina VuorimaaDepartment of Chemistry and Bioengineering, Tampere University of Technology, P. O. Box 541, Korkeakoulunkatu 8, FI33101 Tampere, FinlandPia SiljanderDivision of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5E, 00014 Helsinki, Finland; Division of Biochemistry and Biotechnology, Department of Biosciences, University of Helsinki, P.O. Box 56, Viikinkaari 9, 00014 Helsinki, FinlandMarjo YliperttulaDivision of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5E, 00014 Helsinki, Finland. Electronic address: [email protected]

2015en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1016/j.jconrel.2015.09.031

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Цитирований: 2Использованных источников: 0

Показатели — AkademScholar