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 Supramolecular Nanostructures for Persistent Bioluminescence Imaging of Tumor.

Bioluminescence imaging (BLI) is a powerful technique for noninvasive monitoring of biological processes and cell transplantation. Nonetheless, the application of D-luciferin, which is widely employed as a bioluminescent probe, is restricted in long-term in vivo tracking due to its short half-life. This study presents a novel approach using amino acid-encoded building blocks to accumulate and preserve luciferin within tumor cells, through a supramolecular self-assembly strategy. The building block platform called Cys(SEt)-X-CBT (CXCBT, with X representing any amino acid) utilizes a covalent-noncovalent hybrid self-assembly mechanism to generate diverse luciferin-containing nanostructures in tumor cells after glutathione reduction. These nanostructures exhibit efficient tumor-targeted delivery as well as sequence-dependent well-designed morphologies and prolonged bioluminescence performance. Among the selected amino acids (X = Glu, Lys, Leu, Phe), Cys(SEt)-Lys-CBT (CKCBT) exhibits the superior long-lasting bioluminescence signal (up to 72 h) and good biocompatibility. This study demonstrates the potential of amino-acid-encoded supramolecular self-assembly as a convenient and effective method for developing BLI probes for long-term biological tracking and disease imaging.