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Tumour targeting with rationally modified cell penetrating peptides
Stockholm University, Faculty of Science, Department of Neurochemistry.
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2012 (English)In: International Journal of Peptide Research and Therapeutics, ISSN 1573-3149, Vol. 18, no 4, 361-371 p.Article in journal (Refereed) Published
Abstract [en]

Cell-penetrating peptides (CPPs) are short transport peptides with a well-established ability for delivery of bioactive cargoes inside the cells both, in vitro and in vivo. CPPs enter unselectively in a wide variety of cell lines, this is a desirable property for most in vitro applications, however, in vivo e.g. in tumor models, specific targeted accumulation is required. In order to achieve tumor targeting, a known CPP, YTA4, was modified by prolonging it C-terminally with mainly negatively charged amino acids. Additionally, a matrix metalloproteinase-2 cleavage site was introduced between the CPP and the inactivating sequence. This new peptide, named NoPe, is an inactive pro-form of YTA4. It can be selectively cleaved and thereby activated by MMPs. We have conjugated an imaging agent, fluoresceinyl carboxylic acid, and a cytostatic agent methotrexate, to this activable pro-form. NoPe activation was demonstrated in vitro by recombinant MMP-2 cleavage and the cleavage of the attenuating sequence was abolished with MMP-2 specific inhibitor. Furthermore, the fluoresceinyl-NoPe is selectively accumulated in the tumor tissue in MDA-MB-231 tumor bearing mice after intravenous injection. Thus, this strategy proves to be successful for in vivo tumor imaging.

Place, publisher, year, edition, pages
2012. Vol. 18, no 4, 361-371 p.
Keyword [en]
Cell-penetrating peptide, Targeting, Imaging, Matrix metalloproteinase
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:su:diva-83050DOI: 10.1007/s10989-012-9312-1ISI: 000310230800011OAI: diva2:573838


Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2015-04-22Bibliographically approved

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Langel, Ülo
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Department of Neurochemistry
Biochemistry and Molecular Biology

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