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Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia.

Publication ,  Journal Article
Meyer, DE; Kong, GA; Dewhirst, MW; Zalutsky, MR; Chilkoti, A
Published in: Cancer Res
February 15, 2001

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

February 15, 2001

Volume

61

Issue

4

Start / End Page

1548 / 1554

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Temperature
  • Protein Engineering
  • Peptides
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Microscopy, Video
  • Microscopy, Fluorescence
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Meyer, D. E., Kong, G. A., Dewhirst, M. W., Zalutsky, M. R., & Chilkoti, A. (2001). Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia. Cancer Res, 61(4), 1548–1554.
Meyer, D. E., G. A. Kong, M. W. Dewhirst, M. R. Zalutsky, and A. Chilkoti. “Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia.Cancer Res 61, no. 4 (February 15, 2001): 1548–54.
Meyer DE, Kong GA, Dewhirst MW, Zalutsky MR, Chilkoti A. Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia. Cancer Res. 2001 Feb 15;61(4):1548–54.
Meyer, D. E., et al. “Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia.Cancer Res, vol. 61, no. 4, Feb. 2001, pp. 1548–54.
Meyer DE, Kong GA, Dewhirst MW, Zalutsky MR, Chilkoti A. Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia. Cancer Res. 2001 Feb 15;61(4):1548–1554.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

February 15, 2001

Volume

61

Issue

4

Start / End Page

1548 / 1554

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Temperature
  • Protein Engineering
  • Peptides
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Microscopy, Video
  • Microscopy, Fluorescence