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Enhanced uptake of a thermally responsive polypeptide by tumor cells in response to its hyperthermia-mediated phase transition.

Publication ,  Journal Article
Raucher, D; Chilkoti, A
Published in: Cancer research
October 2001

Elastin-like polypeptides (ELPs) composed of a VPGXG repeat undergo a reversible phase transition in aqueous solution. They are hydrophilic and soluble in aqueous solution below their transition temperature (T(t)), but they become hydrophobic and aggregate when the temperature is raised above their T(t). In this study, we examine the quantitative uptake of a fluorescence-labeled, thermally responsive ELP as a function of ELP concentration between 5 and 15 microM in solution in response to hyperthermia by three cultured cancer cell lines. Flow cytometry of fluorescein-ELP conjugates showed that hyperthermia enhanced the cellular uptake of the thermally responsive ELP in human ovarian carcinoma cells (SKOV-3) and in HeLa cells at a concentration of 10 microM or higher, but not at a concentration of 5 microM, as compared with the uptake of a thermally inactive ELP control. In FaDu cells, hyperthermia stimulated uptake of the thermally responsive ELP at all solution concentrations of ELP between 5 and 15 microM. In particular, a >2-fold greater uptake of thermally responsive ELP compared with the thermally inactive control ELP was observed for FaDu cells at a solution concentration of 15 microM in heated cells. Confocal fluorescence microscopy of tumor cells incubated with a rhodamine conjugate of the thermally responsive ELP showed that the cytoplasm was uniformly stained below the T(t). Above the T(t), fluorescent particles were observed in the cytoplasm, suggesting that these particles are aggregates of the thermally responsive polypeptide resulting from the ELP phase transition. These studies demonstrate that the endocytotic uptake of a thermally responsive ELP is significantly enhanced by the thermally triggered phase transition of the polypeptide.

Duke Scholars

Published In

Cancer research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

October 2001

Volume

61

Issue

19

Start / End Page

7163 / 7170

Related Subject Headings

  • Tumor Cells, Cultured
  • Subcellular Fractions
  • Peptides
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Microscopy, Confocal
  • Kinetics
  • Hyperthermia, Induced
  • Humans
  • Hot Temperature
 

Citation

APA
Chicago
ICMJE
MLA
NLM

Published In

Cancer research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

October 2001

Volume

61

Issue

19

Start / End Page

7163 / 7170

Related Subject Headings

  • Tumor Cells, Cultured
  • Subcellular Fractions
  • Peptides
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Microscopy, Confocal
  • Kinetics
  • Hyperthermia, Induced
  • Humans
  • Hot Temperature