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Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors.

Publication ,  Journal Article
Furgeson, DY; Dreher, MR; Chilkoti, A
Published in: Journal of controlled release : official journal of the Controlled Release Society
January 2006

A thermoresponsive, genetically engineered, elastin-like polypeptide (ELP) containing a C-terminal cysteine residue was synthesized and purified by inverse transition cycling (ITC) and conjugated to doxorubicin (Dox) molecules through four different pH-sensitive, maleimide-activated, hydrazone linkers. The efficiency of Dox activation, conjugation ratios to ELP and biophysical characterization-hydrodynamic radius (Rh) and the temperature transition kinetics-of the ELP-Dox conjugates and pH-mediated release of Dox were quantified in this study. Conjugation ratios of the maleimide-activated Dox to the thiol group of a unique cysteine in the ELP were close to unity. The Rh of the conjugate increased as the linker length between the ELP backbone and Dox was increased. The linker structure and length had little effect on the Tt of the ELP-Dox conjugates, as all conjugates exhibited Tt's that were similar to the native ELP. However, the ELP-Dox conjugates with longer linkers exhibited slower transition kinetics compared to the ELP-Dox conjugates with shorter linkers. The highest release of the ELP-Dox conjugate by cleavage of the hydrazone bond at pH 4 was nearly 80% over 72 h and was exhibited by the conjugate with the shortest linker.

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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

January 2006

Volume

110

Issue

2

Start / End Page

362 / 369

Related Subject Headings

  • Spectrophotometry, Ultraviolet
  • Scattering, Radiation
  • Protein Engineering
  • Pharmacology & Pharmacy
  • Peptides
  • Neoplasms
  • Maleimides
  • Light
  • Hydrogen-Ion Concentration
  • Hydrazones
 

Citation

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Furgeson, D. Y., Dreher, M. R., & Chilkoti, A. (2006). Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors. Journal of Controlled Release : Official Journal of the Controlled Release Society, 110(2), 362–369. https://doi.org/10.1016/j.jconrel.2005.10.006
Furgeson, Darin Y., Matthew R. Dreher, and Ashutosh Chilkoti. “Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors.Journal of Controlled Release : Official Journal of the Controlled Release Society 110, no. 2 (January 2006): 362–69. https://doi.org/10.1016/j.jconrel.2005.10.006.
Furgeson DY, Dreher MR, Chilkoti A. Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors. Journal of controlled release : official journal of the Controlled Release Society. 2006 Jan;110(2):362–9.
Furgeson, Darin Y., et al. “Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors.Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 110, no. 2, Jan. 2006, pp. 362–69. Epmc, doi:10.1016/j.jconrel.2005.10.006.
Furgeson DY, Dreher MR, Chilkoti A. Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors. Journal of controlled release : official journal of the Controlled Release Society. 2006 Jan;110(2):362–369.
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

January 2006

Volume

110

Issue

2

Start / End Page

362 / 369

Related Subject Headings

  • Spectrophotometry, Ultraviolet
  • Scattering, Radiation
  • Protein Engineering
  • Pharmacology & Pharmacy
  • Peptides
  • Neoplasms
  • Maleimides
  • Light
  • Hydrogen-Ion Concentration
  • Hydrazones