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Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors.

Publication ,  Journal Article
Dreher, MR; Liu, W; Michelich, CR; Dewhirst, MW; Chilkoti, A
Published in: Cancer Res
May 1, 2007

The delivery of anticancer therapeutics to solid tumors remains a critical problem in the treatment of cancer. This study reports a new methodology to target a temperature-responsive macromolecular drug carrier, an elastin-like polypeptide (ELP) to solid tumors. Using a dorsal skin fold window chamber model and intravital laser scanning confocal microscopy, we show that the ELP forms micron-sized aggregates that adhere to the tumor vasculature only when tumors are heated to 41.5 degrees C. Upon return to normothermia, the vascular particles dissolve into the plasma, increasing the vascular concentration, which drives more ELPs across the tumor blood vessel and significantly increases its extravascular accumulation. These observations suggested that thermal cycling of tumors would increase the exposure of tumor cells to ELP drug carriers. We investigated this hypothesis in this study by thermally cycling an implanted tumor in nude mice from body temperature to 41.5 degrees C thrice within 1.5 h, and showed the repeated formation of adherent microparticles of ELP in the heated tumor vasculature in each thermal cycle. These results suggest that thermal cycling of tumors can be repeated multiple times to further increase the accumulation of a thermally responsive polymeric drug carrier in solid tumors over a single heat-cool cycle. More broadly, this study shows a new approach--tumor thermal cycling--to exploit stimuli-responsive polymers in vivo to target the tumor vasculature or extravascular compartment with high specificity.

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

May 1, 2007

Volume

67

Issue

9

Start / End Page

4418 / 4424

Location

United States

Related Subject Headings

  • Quinolinium Compounds
  • Peptides
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Hyperthermia, Induced
  • Hydrazines
  • Humans
  • Elastin
 

Citation

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Dreher, M. R., Liu, W., Michelich, C. R., Dewhirst, M. W., & Chilkoti, A. (2007). Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors. Cancer Res, 67(9), 4418–4424. https://doi.org/10.1158/0008-5472.CAN-06-4444
Dreher, Matthew R., Wenge Liu, Charles R. Michelich, Mark W. Dewhirst, and Ashutosh Chilkoti. “Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors.Cancer Res 67, no. 9 (May 1, 2007): 4418–24. https://doi.org/10.1158/0008-5472.CAN-06-4444.
Dreher MR, Liu W, Michelich CR, Dewhirst MW, Chilkoti A. Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors. Cancer Res. 2007 May 1;67(9):4418–24.
Dreher, Matthew R., et al. “Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors.Cancer Res, vol. 67, no. 9, May 2007, pp. 4418–24. Pubmed, doi:10.1158/0008-5472.CAN-06-4444.
Dreher MR, Liu W, Michelich CR, Dewhirst MW, Chilkoti A. Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors. Cancer Res. 2007 May 1;67(9):4418–4424.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

May 1, 2007

Volume

67

Issue

9

Start / End Page

4418 / 4424

Location

United States

Related Subject Headings

  • Quinolinium Compounds
  • Peptides
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Hyperthermia, Induced
  • Hydrazines
  • Humans
  • Elastin