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

JOURNAL OF CONTROLLED RELEASE

卷:284

Review

Saari, H.¹  Lisitsyna, E.^1,2  Rautaniemi, K.²  Rojalin, T.^1,4  Niemi, L.^1,5  Nivaro, O.¹  Laaksonen, T.^1,2  Yliperttula, M.^1,3  Vuorimaa-Laukkanen, E.² 

[1] Univ Helsinki, Div Pharmaceut Biosci, Fac Pharm, FIN-00014 Helsinki, Finland

[2] Tampere Univ Technol, Lab Chem & Bioengn, Tampere 33720, Finland

[3] Univ Padua, Dept Pharmaceut & Pharmacol Sci, Pharmaceut Technol & Biopharmaceut, Via F Marzolo 5, I-35131 Padua, Italy

[4] Univ Calif Davis, Dept Biochem & Mol Med, Sacramento, CA 95817 USA

[5] Orion Pharma, Espoo, Finland

关键词: Extracellular vesicles;    Microvesicles;    Exosomes;    Paclitaxel;    Drug delivery;    Prostate;    Cancer;    Fluorescence lifetime imaging microscopy;   

DOI  :  10.1016/j.jconrel.2018.06.015

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free