Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells
Open accessAbstract
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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Tumor cell-derived exosomes can be a useful vehicle for paclitaxel from the parental cell, carrying the drug into recipient cells through endocytosis and increasing cytotoxicity.
“For example, Saari et al. showed that tumor cell-derived exosomes could be considered a useful vehicle for paclitaxel from the parental cell, carrying the drug into recipient cells through the endocytosis pathway and increasing their cytotoxicity [56].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [56]
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- Authors
- Saari, H., Lázaro-Ibáñez, E., Viitala, T., Vuorimaa-Laukkanen, E., Siljander, P., & Yliperttula, M.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Yliperttula, Marjo
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 220
- Issue
- Pt B
- Pages
- 727-737
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W1787140000
- Cited by
- 613
- References
- 30
- Citations by year
- 2026: 30 · 2025: 58 · 2024: 80 · 2023: 70 · 2022: 80 · 2021: 81 · 2020: 72 · 2019: 47 · 2018: 44 · 2017: 33 · 2016: 18
- FWCI
- 13.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- Finnish Cultural Foundation (00130502)
- K. Albin Johanssons Stiftelse
- Oskar Öflunds Stiftelse
- Academy of Finland (259990)
- Magnus Ehrnrooth Foundation
- Otto A. Malm Foundation
- Medicinska Understödsföreningen Liv och Hälsa
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- extracellular vesicles, microvesicles, exosomes, paclitaxel, drug delivery, prostate cancer, autologous cells, endocytosis, cytotoxicity, LNCaP cells, PC-3 cells
- MeSH terms
- Antineoplastic Agents, Phytogenic, Cell Survival, Chemistry, Pharmaceutical, Dose-Response Relationship, Drug, Drug Carriers, Endocytosis, Humans, Male, Phenotype, Prostatic Neoplasms, Time Factors, Paclitaxel, Cell Line, Tumor, Nanoparticles, Cell-Derived Microparticles, Exosomes
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