Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins
File(s)FuhrmannG-JContRel-2015-acc-ver.docx (4.67 MB)
Accepted version
Author(s)
Fuhrmann, G
Serio, A
Mazo, M
Nair, R
Stevens, MM
Type
Journal Article
Abstract
Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by > 60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods.
Date Issued
2015-05-10
Date Acceptance
2014-11-24
Citation
Journal of Controlled Release, 2015, 205, pp.35-44
ISSN
1873-4995
Publisher
Elsevier
Start Page
35
End Page
44
Journal / Book Title
Journal of Controlled Release
Volume
205
Copyright Statement
© 2014, Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Subjects
Science & Technology
Physical Sciences
Life Sciences & Biomedicine
Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Chemistry
Exosomes
Shedding microvesicles
Drug loading
Porphyrins
Photodynamic therapy
High-content imaging
DRUG-DELIVERY
MEMBRANE-VESICLES
STEM-CELL
IN-VITRO
EXOSOMES
MICROVESICLES
MICRORNA
BRAIN
SIRNA
Publication Status
Published