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Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy.

Publication ,  Journal Article
Dreher, MR; Raucher, D; Balu, N; Michael Colvin, O; Ludeman, SM; Chilkoti, A
Published in: Journal of controlled release : official journal of the Controlled Release Society
August 2003

Thermally responsive elastin-like polypeptides (ELPs) were synthesized by recombinant DNA techniques and conjugated to doxorubicin through an acid-labile hydrazone bond to enable release of the drug in the acidic environment of lysosomes. The thermal properties, intracellular localization and cytotoxicity of the conjugate were investigated in this study. The conjugation procedure resulted in a mixed population of free ELP and ELP-doxorubicin (ELP-dox) conjugates that exhibit a broader transition than the parent ELP. A simple centrifugation procedure was developed to purify the ELP-dox conjugate from other reactants and resulted in a sharper thermal transition, similar to the parent ELP. The ELP was endocytosed by squamous cell carcinoma cells (FaDu) and trafficked into lysosomes, as observed by the colocalization of the ELP with a lysosome-specific dye through confocal fluorescence microscopy. Interestingly, both the ELP-dox conjugate and free drug exhibited near equivalent in vitro cytotoxicity, although their subcellular localization was significantly different. The free drug was largely concentrated in the nucleus, while the conjugate was dispersed throughout the cytoplasm with limited nuclear accumulation. These differences are significant because they suggest a different mechanism of cytotoxicity for the conjugate as compared with the free drug.

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Published In

Journal of controlled release : official journal of the Controlled Release Society

DOI

EISSN

1873-4995

ISSN

0168-3659

Publication Date

August 2003

Volume

91

Issue

1-2

Start / End Page

31 / 43

Related Subject Headings

  • Tumor Cells, Cultured
  • Thermodynamics
  • Pharmacology & Pharmacy
  • Peptides
  • Neoplasms
  • Microscopy, Confocal
  • Hydrazones
  • Humans
  • Elastin
  • Doxorubicin
 

Citation

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ICMJE
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Dreher, M. R., Raucher, D., Balu, N., Michael Colvin, O., Ludeman, S. M., & Chilkoti, A. (2003). Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy. Journal of Controlled Release : Official Journal of the Controlled Release Society, 91(1–2), 31–43. https://doi.org/10.1016/s0168-3659(03)00216-5
Dreher, Matthew R., Drazen Raucher, Narayanan Balu, O. Michael Colvin, Susan M. Ludeman, and Ashutosh Chilkoti. “Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy.Journal of Controlled Release : Official Journal of the Controlled Release Society 91, no. 1–2 (August 2003): 31–43. https://doi.org/10.1016/s0168-3659(03)00216-5.
Dreher MR, Raucher D, Balu N, Michael Colvin O, Ludeman SM, Chilkoti A. Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy. Journal of controlled release : official journal of the Controlled Release Society. 2003 Aug;91(1–2):31–43.
Dreher, Matthew R., et al. “Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy.Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 91, no. 1–2, Aug. 2003, pp. 31–43. Epmc, doi:10.1016/s0168-3659(03)00216-5.
Dreher MR, Raucher D, Balu N, Michael Colvin O, Ludeman SM, Chilkoti A. Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy. Journal of controlled release : official journal of the Controlled Release Society. 2003 Aug;91(1–2):31–43.
Journal cover image

Published In

Journal of controlled release : official journal of the Controlled Release Society

DOI

EISSN

1873-4995

ISSN

0168-3659

Publication Date

August 2003

Volume

91

Issue

1-2

Start / End Page

31 / 43

Related Subject Headings

  • Tumor Cells, Cultured
  • Thermodynamics
  • Pharmacology & Pharmacy
  • Peptides
  • Neoplasms
  • Microscopy, Confocal
  • Hydrazones
  • Humans
  • Elastin
  • Doxorubicin