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Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model.

Publication ,  Journal Article
Liu, W; MacKay, JA; Dreher, MR; Chen, M; McDaniel, JR; Simnick, AJ; Callahan, DJ; Zalutsky, MR; Chilkoti, A
Published in: J Control Release
May 21, 2010

This study evaluated a biodegradable drug delivery system for local cancer radiotherapy consisting of a thermally sensitive elastin-like polypeptide (ELP) conjugated to a therapeutic radionuclide. Two ELPs (49 kDa) were synthesized using genetic engineering to test the hypothesis that injectable biopolymeric depots can retain radionuclides locally and reduce the growth of tumors. A thermally sensitive polypeptide, ELP(1), was designed to spontaneously undergo a soluble-insoluble phase transition (forming viscous microparticles) between room temperature and body temperature upon intratumoral injection, while ELP(2) was designed to remain soluble upon injection and to serve as a negative control for the effect of aggregate assembly. After intratumoral administration of radionuclide conjugates of ELPs into implanted tumor xenografts in nude mice, their retention within the tumor, spatio-temporal distribution, and therapeutic effect were quantified. The residence time of the radionuclide-ELP(1) in the tumor was significantly longer than the thermally insensitive ELP(2) conjugate. In addition, the thermal transition of ELP(1) significantly protected the conjugated radionuclide from dehalogenation, whereas the conjugated radionuclide on ELP(2) was quickly eliminated from the tumor and cleaved from the biopolymer. These attributes of the thermally sensitive ELP(1) depot improved the antitumor efficacy of iodine-131 compared to the soluble ELP(2) control. This novel injectable and biodegradable depot has the potential to control advanced-stage cancers by reducing the bulk of inoperable tumors, enabling surgical removal of de-bulked tumors, and preserving healthy tissues.

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Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

May 21, 2010

Volume

144

Issue

1

Start / End Page

2 / 9

Location

Netherlands

Related Subject Headings

  • Radioisotopes
  • Pharmacology & Pharmacy
  • Peptides
  • Neoplastic Processes
  • Neoplasms
  • Mice, Nude
  • Mice
  • Injections
  • Hot Temperature
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Liu, W., MacKay, J. A., Dreher, M. R., Chen, M., McDaniel, J. R., Simnick, A. J., … Chilkoti, A. (2010). Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model. J Control Release, 144(1), 2–9. https://doi.org/10.1016/j.jconrel.2010.01.032
Liu, Wenge, J Andrew MacKay, Matthew R. Dreher, Mingnan Chen, Jonathan R. McDaniel, Andrew J. Simnick, Daniel J. Callahan, Michael R. Zalutsky, and Ashutosh Chilkoti. “Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model.J Control Release 144, no. 1 (May 21, 2010): 2–9. https://doi.org/10.1016/j.jconrel.2010.01.032.
Liu W, MacKay JA, Dreher MR, Chen M, McDaniel JR, Simnick AJ, et al. Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model. J Control Release. 2010 May 21;144(1):2–9.
Liu, Wenge, et al. “Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model.J Control Release, vol. 144, no. 1, May 2010, pp. 2–9. Pubmed, doi:10.1016/j.jconrel.2010.01.032.
Liu W, MacKay JA, Dreher MR, Chen M, McDaniel JR, Simnick AJ, Callahan DJ, Zalutsky MR, Chilkoti A. Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model. J Control Release. 2010 May 21;144(1):2–9.
Journal cover image

Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

May 21, 2010

Volume

144

Issue

1

Start / End Page

2 / 9

Location

Netherlands

Related Subject Headings

  • Radioisotopes
  • Pharmacology & Pharmacy
  • Peptides
  • Neoplastic Processes
  • Neoplasms
  • Mice, Nude
  • Mice
  • Injections
  • Hot Temperature
  • Female