Recent advances in drug delivery systems based on polypeptides prepared from N-carboxyanhydrides

Multifunctional polypeptide-based drug delivery systems prepared from ring-opening polymerization of N-carboxyanhydrides demonstrate enormous potential in the drug delivery field, incorporating increased biostability along with stimuli-responsive and active targeting functions. Recent years have seen a dramatic increase in interest in the use of ring-opening polymerization of N-carboxyanhydride monomers as a method to prepare well-defined polypeptides and peptide hybrid materials. The resulting molecules are often capable of assembling into a variety of different structures, including micelles, vesicles, nanoparticles and hydrogels, and therefore have been explored as novel drug delivery systems. Peptides are attractive in this regard due to their rich chemical functionality and ability to assemble through the formation of secondary structures (e.g. α-helices and β-sheets). In addition, they are inherently biodegradable and biocompatible. This review describes recent advances in the field, covering aspects such as improved methods with which to prepare better-defined polypeptides, crosslinking of assemblies to enhance biostability, the preparation of materials that respond to a variety of stimuli (including light and intra- or extracellular redox conditions), functionalization with targeting ligands to enhance cellular uptake, assemblies for small interfering RNA delivery and approaches to theranostic systems.