| Effective tumor targeting and enhanced anti-tumor effect of liposomes engrafted with peptides specific for tumor lymphatics and vasculature. | |
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MedLine Citation:
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PMID: 21443937 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The use of liposomes to target drugs to tumors represents an attractive therapeutic strategy, especially when used with convenient targeting moieties such as peptides. Here we explored several peptides for their ability to target liposomes to tumors. The metal chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA(3)-DTDA) was incorporated into liposomes to enable the engraftment of His-tagged peptides containing targeting motifs specific for tumor vasculature markers VEGFR-1 (p39-Flt-1) and neuropilin-1 (p24-NRP-1), or a motif known to accumulate in hypoxic areas of tumors (p47-LyP-1). Peptide-engrafted liposomes were examined for their biodistribution and anti-tumor effects after i.v. administration. Our results show that radiolabelled liposomes engrafted with either p24-NRP-1 or p47-LyP-1 and then injected into mice bearing subcutaneous B16-F1 tumors, show increased accumulation in the tumor. For p24-NRP-1-liposomes, tumor targeting was significantly increased when the stabilizing lipid phosphatidylethanolamine polyethylene glycol-750 (PE-PEG(750)) was used instead of PE-PEG(2000) in the liposome lipid mixture. Importantly, compared to the controls, p24-NRP-1 liposomes containing 10 mol% PE-PEG(750) and loaded with doxorubicin significantly inhibited the rate of tumor growth of the tumor-bearing mice. Our findings demonstrate that the use of drug-containing liposomes incorporating NTA(3)-DTDA and engrafted with NRP-1 targeting peptide is a convenient strategy to enhance the therapeutic effect of non-targeted doxorubicin. |
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Authors:
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Thomas P Herringson; Joseph G Altin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-25 |
Journal Detail:
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Title: International journal of pharmaceutics Volume: - ISSN: 1873-3476 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Division of Biomedical Science and Biochemistry, Research School of Biology, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, 0200, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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