| A cyclic-RGD-BioShuttle functionalized with TMZ by DARinv "Click Chemistry" targeted to αvβ3 integrin for therapy. | |
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MedLine Citation:
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PMID: 20922134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Clinical experiences often document, that a successful tumor control requires high doses of drug applications. It is widely believed that unavoidable adverse reactions could be minimized by using gene-therapeutic strategies protecting the tumor-surrounding healthy tissue as well as the bone-marrow. One new approach in this direction is the use of "Targeted Therapies" realizing a selective drug targeting to gain effectual amounts at the target site, even with drastically reduced application doses. MCF-7 breast cancer cells expressing the α(v)β(3) [alpha(v)beta(3)] integrin receptor are considered as appropriate candidates for such a targeted therapy. The modularly composed BioShuttle carrier consisting of different units designed to facilitate the passage across the cell membranes and for subcellular addressing of diagnostic and/or therapeutic molecules could be considered as an eligible delivery platform. Here we used the cyclic RGD-BioShuttle as a carrier for temozolomide (TMZ) at the α(v)β(3) integrin receptor realizing local TMZ concentrations sufficient for cell killing. The IC50 values are 12 µMol/L in the case of cRGD-BioShuttle-TMZ and 100 µMol/L for underivatized TMZ, which confirms the advantage of TMZ reformulation to realize local concentrations sufficient for cell killing. Our paper focuses on the design, synthesis and application of the cRGD-BioShuttle conjugate composed of the cyclic RGD, a α(v)β(3) integrin-ligand, ligated to the cytotoxic drug TMZ. The ligation was carried out by the Diels Alder Reaction with inverse electron demand (DAR(inv)). |
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Authors:
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Klaus Braun; Manfred Wiessler; Rüdiger Pipkorn; Volker Ehemann; Tobias Bäuerle; Heinz Fleischhacker; Gabriele Müller; Peter Lorenz; Waldemar Waldeck |
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Publication Detail:
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Type: Journal Article Date: 2010-09-21 |
Journal Detail:
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Title: International journal of medical sciences Volume: 7 ISSN: 1449-1907 ISO Abbreviation: Int J Med Sci Publication Date: 2010 |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2011-01-24 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 101213954 Medline TA: Int J Med Sci Country: Australia |
Other Details:
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Languages: eng Pagination: 326-39 Citation Subset: IM |
Affiliation:
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German Cancer Research Center, Dept. of Imaging and Radiooncology, INF 280, D-69120 Heidelberg, Germany. k.braun@dkfz.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Alkylating
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chemistry*,
pharmacokinetics,
therapeutic use* Breast Neoplasms / drug therapy Cell Line, Tumor Cell Size / drug effects Dacarbazine / analogs & derivatives*, chemistry, pharmacokinetics, therapeutic use Female Flow Cytometry HeLa Cells Humans Inhibitory Concentration 50 Integrin alphaVbeta3 / antagonists & inhibitors*, metabolism Microscopy, Confocal Peptides, Cyclic / chemistry* Uterine Cervical Neoplasms / drug therapy |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 0/Integrin alphaVbeta3; 0/Peptides, Cyclic; 0/cyclic arginine-glycine-aspartic acid peptide; 4342-03-4/Dacarbazine; 85622-93-1/temozolomide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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