Temperature sensitive peptides: Engineering hyperthermia-directed therapeutics

Abstract

Purpose. 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. Analysis. 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 (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. Conclusions. Temperature sensitive peptides are a powerful engineering platform that will enable new strategies for hyperthermia-directed drug delivery.