Document Detail

Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia.
MedLine Citation:
PMID:  11245464     Owner:  NLM     Status:  MEDLINE    
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.
D E Meyer; G A Kong; M W Dewhirst; M R Zalutsky; A Chilkoti
Related Documents :
19729214 - Can hypoxia-pet map hypoxic cell density heterogeneity accurately in an animal tumor mo...
2247594 - Effect of step-down heating on brachytherapy in a murine tumor system.
8270614 - Oxygenation of tumors by a hemoglobin solution.
9088144 - Oxygen and cancer.
23909414 - Correlation between clinical features, imaging and pathologic findings in recurrent sol...
15604264 - Conditional rock activation in vivo induces tumor cell dissemination and angiogenesis.
Publication Detail:
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:
Title:  Cancer research     Volume:  61     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-13     Completed Date:  2001-03-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1548-54     Citation Subset:  IM    
Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Sequence
Base Sequence
Drug Stability
Elastin / chemistry,  genetics,  pharmacokinetics*
Glioma / metabolism*
Hyperthermia, Induced*
Mice, Inbred BALB C
Mice, Nude
Microscopy, Fluorescence
Microscopy, Video
Molecular Sequence Data
Ovarian Neoplasms / metabolism*
Peptides / chemistry,  genetics,  pharmacokinetics*
Protein Engineering
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/Peptides; 9007-58-3/Elastin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis b...
Next Document:  Antibodies elicited by naked DNA vaccination against the complementary-determining region 3 hypervar...