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 organization: Faculty of Pharmacy
Division of Pharmaceutical Biosciences
Drug Research Program
Doctoral Programme in Drug Research
Doctoral Programme in Materials Research and Nanosciences
Nanobio Pharmaceutics
Biopharmaceutics Group
Date: 2018-08-28
Language: eng
Number of pages: 11
Belongs to series: Journal of Controlled Release
ISSN: 0168-3659
DOI: https://doi.org/10.1016/j.jconrel.2018.06.015
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
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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