Covalently triggered self-assembly of peptide-based nanodrugs for cancer theranostics

Covalently triggered peptide self-assembly is achieved through sequential inte-gration of spontaneous covalent reaction and noncovalent interactions, thus both enhancing the physiological stability and extending unexpected function-ality of the resulting peptide-based assemblies, different from popular supramo-lecular peptide self-assembly merely associated with noncovalent interactions. This review summarizes the recent progress on the development of covalently triggered peptide self-assembly for cancer theranostics. Especially, we propose the fundamental design principle of covalently triggered peptide self-assembly for constructing a variety of peptide-based assemblies including nanoparticles, nanofibers, hollow nanospheres, and other nanoarchitectures. Subsequently, the discussion is anchored in an overview of representative covalently assembled peptide-based nanodrugs for the cancer theranostics. Finally, the challenges and perspectives on the clinical potential of the covalently assembled peptide-based nanodrugs are highlighted. This review will provide new insights into construc-tion of peptide-based nanodrugs through combination of covalent reaction and noncovalent self-assembly and prompt their clinical applications in cancer diag-nosis and therapeutics.