| Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia. | |
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MedLine Citation:
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PMID: 11245464 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Elastin-like polypeptides (ELPs) are biopolymers of the pentapeptide repeat Val-Pro-Gly-Xaa-Gly that undergo an inverse temperature phase transition. They are soluble in aqueous solutions below their transition temperature (T1) but hydrophobically collapse and aggregate at temperatures greater than T1. We hypothesized that ELPs conjugated to drugs would enable thermally targeted drug delivery to solid tumors if their T1 were between body temperature and the temperature in a locally heated region. To test this hypothesis, we synthesized a thermally responsive ELP with a T1 of 41 degrees C and a thermally unresponsive control ELP in Escherichia coli using recombinant DNA techniques. In vivo fluorescence videomicroscopy and radiolabel distribution studies of ELP delivery to human tumors (SKOV-3 ovarian carcinoma and D-54MG glioma) implanted in nude mice demonstrated that hyperthermic targeting of the thermally responsive ELP for 1 h provides a approximately 2-fold increase in tumor localization compared to the same polypeptide without hyperthermia. We observed aggregates of the thermally responsive ELP by fluorescence videomicroscopy within the heated tumor microvasculature but not in control experiments, which demonstrates that the phase transition of the thermally responsive ELP carrier can be engineered to occur in vivo at a specified temperature. By exploiting the phase transition-induced aggregation of these polypeptides, this method provides a new way to thermally target polymer-drug conjugates to solid tumors. |
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Authors:
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D E Meyer; G A Kong; M W Dewhirst; M R Zalutsky; A Chilkoti |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 61 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-03-13 Completed Date: 2001-03-29 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 1548-54 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Sequence Drug Stability Elastin / chemistry, genetics, pharmacokinetics* Female Glioma / metabolism* Humans Hyperthermia, Induced* Mice Mice, Inbred BALB C Mice, Nude Microscopy, Fluorescence Microscopy, Video Molecular Sequence Data Ovarian Neoplasms / metabolism* Peptides / chemistry, genetics, pharmacokinetics* Protein Engineering Temperature Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
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CA42745/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Peptides; 9007-58-3/Elastin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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