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

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http://hdl.handle.net/10138/239089

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Saari , H , Lisitsyna , E S , Rautaniemi , K , Rojalin , T , Niemi , L , Nivaro , O , Laaksonen , T , Yliperttula , M & Vuorimaa-Laukkanen , E 2018 , ' FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel ' , Journal of Controlled Release , vol. 284 , pp. 133-143 . https://doi.org/10.1016/j.jconrel.2018.06.015

Title: FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel
Author: Saari, H.; Lisitsyna, Ekaterina S.; Rautaniemi, K.; Rojalin, T.; Niemi, L.; Nivaro, O.; Laaksonen, T.; Yliperttula, M.; Vuorimaa-Laukkanen, E.
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Drug Research Program
University of Helsinki, Drug Research Program
Date: 2018-08-28
Language: eng
Number of pages: 11
Belongs to series: Journal of Controlled Release
ISSN: 0168-3659
URI: http://hdl.handle.net/10138/239089
Abstract: 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.
Subject: Extracellular vesicles
Microvesicles
Exosomes
Paclitaxel
Drug delivery
Prostate
Cancer
Fluorescence lifetime imaging microscopy
PLASMON RESONANCE SPECTROSCOPY
LIFETIME IMAGING MICROSCOPY
EXTRACELLULAR VESICLES
DRUG-DELIVERY
CANCER CELLS
FLUORESCENCE MICROSCOPY
INFECTIOUS-DISEASES
MEMBRANE-VESICLES
IMMUNE-RESPONSES
EMERGING ROLE
317 Pharmacy
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