Light-modulated kinetic control of covalent-supramolecular gradients for the assembly of hollow peptide nanostructures

Covalent peptide assembly through integrating robust covalent bonds with dynamic non-covalent interactions offers a promising strategy for creating stable long-lasting assemblies with novel functionalities. However, significant challenges remain in understanding the intricate relationship between covalent bond formation kinetics and assembly pathways, as well as in achieving precise structural control and morphological diversity. Herein, we demonstrate kinetically controlled covalent peptide assembly through light-modulated tyrosine photo-crosslinking to fabricate hierarchical hollow nanostructures. Modulating the light intensity induces spatial inhomogeneity within the assemblies by creating covalent-supramolecular gradients that enable unprecedented control over the hierarchy and morphology. Selective dissociation of the non-covalent-supramolecular compartments results in hollow nanoparticles with tunable structural parameters (e.g., size, shell thickness, and cavity dimensions), which is achieved by balancing the covalent and non-covalent domains. This method enables diverse architectures, including bumpy capsules, core-shell, and yolk-shell structures. Furthermore, the co-assembly and biomineralization properties of peptides enable the creation of biotin-functionalized co-assemblies for enzyme immobilization and metal-peptide hybrid nanozymes with photothermal and peroxidase-like catalytic activity. These findings provide crucial insights into hierarchical assembly mechanisms and advance the design of tailored hollow peptide nanostructures for a wide range of applications.