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

Supramolecular 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. Amino-acid-encoded multi-morphological building block platform: A universal building block cysteine (Cys)(SEt)-X-2-cyano-benzothiazole (CBT) is employed here as an ideal platform for building nanostructures with diverse morphologies. After caging the Cys with stimulus-responsive sites and modifying X with probes/drugs, multi-morphological and multi-functional nanocarriers can be easily prepared for a broad range of biomedical applications. image