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

Research output: Contribution to journalReview ArticleScientificpeer-review

Details

Original languageEnglish
Pages (from-to)133-143
Number of pages11
JournalJournal of Controlled Release
Volume284
DOIs
Publication statusPublished - 28 Aug 2018
Publication typeA2 Review article in a scientific journal

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.

ASJC Scopus subject areas

Keywords

  • Cancer, Drug delivery, Exosomes, Extracellular vesicles, Fluorescence lifetime imaging microscopy, Microvesicles, Paclitaxel, Prostate

Publication forum classification

Field of science, Statistics Finland

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