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Temperature sensitive peptides: engineering hyperthermia-directed therapeutics.

Publication ,  Journal Article
Mackay, JA; Chilkoti, A
Published in: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
September 2008

Recent progress suggests that short peptide motifs can be engineered into biopolymers with specific temperature dependent behavior. This review discusses peptide motifs capable of thermo-responsive behavior, and broadly summarizes design approaches that exploit these peptides as drug carriers. This review focuses on one class of thermally responsive peptide-based biopolymers, elastin-like polypeptides in greater detail.Four peptide motifs are presented based on leucine zippers, human collagen, human elastin, and silkworm silk that are potential building blocks for thermally responsive biopolymers. When these short motifs (<7 amino acids) are repeated many times, they generate biopolymers with higher order structure and complex temperature triggered behaviors. These structures are thermodynamically modulated, making them intrinsically temperature sensitive. These four motifs can be categorized by the directionality and reversibility of association. Elastin-like polypeptides (ELPs) are one promising motif that reversibly associates during heating. ELPs aggregate sharply above an inverse phase transition temperature, which depends on polymer hydrophobicity, molecular weight, and concentration. ELPs can be modified with chemotherapeutics, are biodegradable, are biocompatible, have low immunogenicity, and have terminal pharmacokinetic half-lives >8 h. ELP block copolymers can reversibly form micelles in response to hyperthermia, and this behavior can modulate the binding avidity of peptide ligands. When high molecular weight ELPs are systemically administered to mice they accumulate in tumors; furthermore, hyperthermia can initiate the ELP phase transition and double the concentration of peptide in the tumor.Temperature sensitive peptides are a powerful engineering platform that will enable new strategies for hyperthermia-directed drug delivery.

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Published In

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

DOI

EISSN

1464-5157

ISSN

0265-6736

Publication Date

September 2008

Volume

24

Issue

6

Start / End Page

483 / 495

Related Subject Headings

  • Temperature
  • Protein Engineering
  • Peptides
  • Oncology & Carcinogenesis
  • Neoplasms
  • Molecular Sequence Data
  • Hyperthermia, Induced
  • Humans
  • Elastin
  • Drug Carriers
 

Citation

APA
Chicago
ICMJE
MLA
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Mackay, J. A., & Chilkoti, A. (2008). Temperature sensitive peptides: engineering hyperthermia-directed therapeutics. International Journal of Hyperthermia : The Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 24(6), 483–495. https://doi.org/10.1080/02656730802149570
Mackay, J Andrew, and Ashutosh Chilkoti. “Temperature sensitive peptides: engineering hyperthermia-directed therapeutics.International Journal of Hyperthermia : The Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 24, no. 6 (September 2008): 483–95. https://doi.org/10.1080/02656730802149570.
Mackay JA, Chilkoti A. Temperature sensitive peptides: engineering hyperthermia-directed therapeutics. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2008 Sep;24(6):483–95.
Mackay, J. Andrew, and Ashutosh Chilkoti. “Temperature sensitive peptides: engineering hyperthermia-directed therapeutics.International Journal of Hyperthermia : The Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, vol. 24, no. 6, Sept. 2008, pp. 483–95. Epmc, doi:10.1080/02656730802149570.
Mackay JA, Chilkoti A. Temperature sensitive peptides: engineering hyperthermia-directed therapeutics. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2008 Sep;24(6):483–495.

Published In

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

DOI

EISSN

1464-5157

ISSN

0265-6736

Publication Date

September 2008

Volume

24

Issue

6

Start / End Page

483 / 495

Related Subject Headings

  • Temperature
  • Protein Engineering
  • Peptides
  • Oncology & Carcinogenesis
  • Neoplasms
  • Molecular Sequence Data
  • Hyperthermia, Induced
  • Humans
  • Elastin
  • Drug Carriers