Self-Assembly of Noncanonical Peptides: A New Frontier in Cancer Therapeutics and Beyond

In addition to the 20 standard amino acids that form the building blocks of proteins, nature employs alternative amino acids to create specialized "noncanonical peptides." These unique peptides, found in organisms from bacteria to humans, often exhibit unconventional structures and functionalities, playing critical roles in modulating cellular processes, particularly as antibiotics. Their potential has attracted significant interest for designing novel functional materials based on noncanonical peptides. This review highlights recent advances in the generation and application of noncanonical peptide assemblies. It begins with a definition of noncanonical peptides, including classic examples that showcase their distinct structures and useful biological activities. Then the applications of noncanonical peptide assemblies in developing anticancer therapeutics are discussed, focusing on recent and representative studies that demonstrate their efficacy and versatility in targeting tumor cells. Beyond oncology, it is explored how noncanonical peptide assemblies have been utilized in biomaterials, regenerative medicine, molecular imaging and catalysis. Finally, perspectives are offered on future directions in this rapidly evolving field, emphasizing exciting opportunities and remaining challenges that will drive continued innovation in designing and applying noncanonical peptide-based assemblies.