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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 micro-pinocytosed 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.

Titel:	Mitochondrial Routing of Glucose and Sucrose Polymers after Pinocytotic Uptake: Avenues for Drug Delivery
Autor/in / Beteiligte Person:	RASHID, Rafi ; BEYER, Sebastian ; BLOCKI, Anna ; LE VISAGE, Catherine ; TRAU, Dieter ; WOHLAND, Thorsten ; RAGHUNATH, Michael
Link:	View record from PASCAL Archive
Zeitschrift:	Biomacromolecules, Jg. 15 (2014), Heft 6, S. 2119-2127
Veröffentlichung:	Washington, DC: American Chemical Society, 2014
Medientyp:	academicJournal
Umfang:	print, 32 ref
ISSN:	1525-7797 (print)
Schlagwort:	Biochemistry, molecular biology, biophysics Biochimie, biologie moléculaire, biophysique Polymers, paint and wood industries Polymères, industries des peintures et bois Sciences exactes et technologie Exact sciences and technology Sciences appliquees Applied sciences Physicochimie des polymeres Physicochemistry of polymers Polymères d'origine naturelle Natural polymers Amidon et polyosides divers Starch and polysaccharides Activité biologique Biological activity Actividad biológica Cellule mésenchymateuse Mesenchymal cell Célula mesenquimatosa Cellule souche Stem cell Célula primitiva Etude expérimentale Experimental study Estudio experimental Libération Release Liberación Mitochondrie Mitochondria Mitocondria Mécanisme Mechanism Mecanismo Oside polymère Oside polymer Osido polímero Photosensibilisant Photosensitizer Fotosensibilizante Photothérapie dynamique Photodynamic therapy Fototerapia dinamica Pinocytose Pinocytosis Pinocitosis Polymère linéaire Linear polymer Polímero lineal Polymère ramifié Branched polymer Polímero ramificado Polymère vecteur Control release polymer Polímero vector Rose bengale Rose bengal Vecteur médicament Drug carrier Vector medicamento Localisation intracellulaire Pullulane
Sonstiges:	Nachgewiesen in: PASCAL Archive Sprachen: English Original Material: INIST-CNRS Document Type: Article File Description: text Language: English Author Affiliations: NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 117456, Singapore ; NUS Centre for Bioimaging Sciences (CBIS), National University of Singapore, 117557, Singapore ; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117575, Singapore ; NUS Tissue Engineering Programme (NUSTEP), Life Science Institute, National University of Singapore, 117S10, Singapore ; Inserm, U698, Cardiovascular Bio-Engineering Group, Paris 75654, France ; Department of Chemical & Biomolecular Engineering, Faculty of Engineering, National University of Singapore, 117576, Singapore ; Departments of Biological Sciences & Chemistry, Faculty of Science, National University of Singapore, 117543, Singapore ; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore Rights: Copyright 2015 INIST-CNRS ; CC BY 4.0 ; Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS Notes: Physical chemistry of polymers

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Mitochondrial Routing of Glucose and Sucrose Polymers after Pinocytotic Uptake: Avenues for Drug Delivery