Temperature sensitive peptides: engineering hyperthermia-directed therapeutics.

Journal Article (Review;Journal Article)


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.

Full Text

Duke Authors

Cited Authors

  • Mackay, JA; Chilkoti, A

Published Date

  • September 2008

Published In

Volume / Issue

  • 24 / 6

Start / End Page

  • 483 - 495

PubMed ID

  • 18608590

Pubmed Central ID

  • PMC2820342

Electronic International Standard Serial Number (EISSN)

  • 1464-5157

International Standard Serial Number (ISSN)

  • 0265-6736

Digital Object Identifier (DOI)

  • 10.1080/02656730802149570


  • eng