Enzymatic Noncovalent Synthesis of Supramolecular Soft Matter for Biomedical Applications

Enzymatic noncovalent synthesis (ENS), a process that integrates enzymatic reactions and supramolecular (i.e., noncovalent) interactions for spatial organization of higher-order molecular assemblies, represents an emerging research area at the interface of physical and biological sciences. This review provides a few representative examples of ENS in the context of supramolecular soft matter. After a brief comparison of enzymatic covalent and noncovalent synthesis, we discuss ENS of man-made molecules for generating supramolecular nanostructures (e.g., supramolecular hydrogels) in cell-free conditions. Then, we introduce ENS in a cellular environment. To illustrate the unique merits for applications, we discuss intercellular, peri- or intracellular, and subcellular ENS for cell morphogenesis, molecular imaging, cancer therapy, and targeted delivery. Finally, we provide an outlook on the potential of ENS. We hope that this review offers a new perspective for scientists who develop supramolecular soft matter to address societal needs at various frontiers.