Amino‐Acid‐Encoded Bioinspired Supramolecular Self‐Assembly of Multimorphological Nanocarriers

Abstract

AbstractSupramolecular self‐assembly has emerged as an efficient tool to construct well‐organized nanostructures for biomedical applications by small organic molecules. However, the physicochemical properties of self‐assembled nanoarchitectures are greatly influenced by their morphologies, mechanical properties, and working mechanisms, making it challenging to design and screen ideal building blocks. Herein, using a biocompatible firefly‐sourced click reaction between the cyano group of 2‐cyano‐benzothiazole (CBT) and the 1,2‐aminothiol group of cysteine (Cys), an amino‐acid‐encoded supramolecular self‐assembly platform Cys(SEt)‐X‐CBT (X represents any amino acid) is developed to incorporate both covalent and noncovalent interactions for building diverse morphologies of nanostructures with bioinspired response mechanism, providing a convenient and rapid strategy to construct site‐specific nanocarriers for drug delivery, cell imaging, and enzyme encapsulation. Additionally, it is worth noting that the biodegradation of Cys(SEt)‐X‐CBT generated nanocarriers can be easily tracked via bioluminescence imaging. By caging either the thiol or amino groups in Cys with other stimulus‐responsive sites and modifying X with probes or drugs, a variety of multi‐morphological and multifunctional nanomedicines can be readily prepared for a wide range of biomedical applications.