• polypeptides;
  • stimuli-sensitive materials;
  • drug delivery;
  • gene delivery;
  • poly(amino acids)


Stimuli-sensitive synthetic polypeptides are unique biodegradable and biocompatible synthetic polymers with structures mimicking natural proteins. These polymers exhibit reversible secondary conformation transitions and/or hydrophilic–hydrophobic transitions in response to changes in environmental conditions such as pH and temperature. The stimuli-triggered conformation and/or phase transitions lead to unique self-assembly behaviors, making these materials interesting for controlled drug and gene delivery applications. Therefore, stimuli-sensitive synthetic polypeptide-based materials have been extensively investigatid in recent years. Various polypeptide-based materials, including micelles, vesicles, nanogels, and hydrogels, have been developed and tested for drug- and gene-delivery applications. In addition, the presence of reactive side groups in some polypeptides facilitates the incorporation of various functional moieties to the polypeptides. This Review focuses on recent advances in stimuli-sensitive polypeptide-based materials that have been designed and evaluated for drug and gene delivery applications. In addition, recent developments in the preparation of stimuli-sensitive functionalized polypeptides are discussed.