Title: Mitochondrial routing of glucose and sucrose polymers after pinocytotic uptake : avenues for drug delivery
Authors : Rashid, Rafi
Beyer, Sebastian
Blocki, Anna
Le Visage, Catherine
Trau, Dieter
Wohland, Thorsten
Raghunath, Michael
Published in : Biomacromolecules
Volume(Issue) : 15
Issue : 6
Pages : 2119
Pages to: 2127
Publisher / Ed. Institution : American Chemical Society
Issue Date: 2014
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subject (DDC) : 571: Physiology and related subjects
Abstract: Mitochondria are key organelles organizing cellular metabolic flux. Therefore, a targeted drug delivery to mitochondria promises the advancement of medicine in fields that are associated with mitochondrial dysfunction. However, successful mitochondrial drug delivery is limited by complex transport steps across organelle membranes and fast drug efflux in cases of multidrug resistance. Strategies to deliver small-molecular-weight drugs to mitochondria are very limited, while the use of complex polymeric carriers is limited by a lack of clinical feasibility. We show here that clinically established macromolecules such as a sucrose copolymer (Ficoll 70/400 kDa) and polyglucose (dextran 70/500 kDa) are micropinocytosed swiftly by mesenchymal stem cells and subsequently routed to mitochondria. The intracellular level of Ficoll appears to decrease over time, suggesting that it does not persist within cells. After coupling to polysucrose, the low-molecular-weight photodynamic drug Rose Bengal reached mitochondria and thus exhibited an increased destructive potential after laser excitation. These findings support new opportunities to deliver already clinically approved drugs to mitochondria.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific Journal
DOI : 10.1021/bm500243m
ISSN: 1525-7797
URI: https://digitalcollection.zhaw.ch/handle/11475/12193
Appears in Collections:Publikationen Life Sciences und Facility Management

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