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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18984

Marty, C; Meylan, C; Schott, H; Ballmer-Hofer, K; Schwendener, R (2004). Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes. Cellular and Molecular Life Sciences, 61(14):1785-1794.

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Abstract

Protein transduction domains (PTDs) are used to enhance cellular uptake of drugs, proteins, polynucleotides or liposomes. In this study, functionalized Antennapedia (Antp, aa 43-58) and HIV Tat (aa 47-57) peptides were coupled to small unilamellar liposomes via thiol-maleimide linkage. Modified liposomes showed higher uptake into a panel of cell lines including tumor and dendritic cells than unmodified control liposomes. Liposome uptake was time and concentration dependent as analyzed by flow cytometry and live-cell microscopy. At least 100 PTD molecules per small unilamellar liposome (100 +/- 30 nm) were necessary for efficient translocation into cells. Cellular uptake of PTD-modified liposomes was 15- to 25-fold increased compared to unmodified liposomes and was inhibited by preincubation of liposomes with heparin. Glycosaminoglycan-deficient CHO cells showed dramatically reduced cell association of PTD-modified liposomes, confirming the important role of heparan sulfate proteoglycans in PTD-mediated uptake. Antp-liposomes used as carriers of the cytotoxic drug N4-octadecyl-1-beta-D-arabinofuranosylcytosine-(5'- 5')-3'-C-ethinylcytidine showed a reduction of the IC50 by 70% on B16F1 melanoma cells compared with unmodified liposomes. PTD-functionalized liposomes, particularly Antp-liposomes, represent an interesting novel carrier system for enhanced cell-specific delivery of a large variety of liposome-entrapped molecules.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2004
Deposited On:09 Jun 2009 12:56
Last Modified:27 Nov 2013 22:03
Publisher:Springer
ISSN:1420-682X
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:10.1007/s00018-004-4166-0
PubMed ID:15241554
Citations:Web of Science®. Times Cited: 74
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Scopus®. Citation Count: 81

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