ABSTRACT Gold nanoclusters (AuNCs) have garnered significant attention in biomedicine. Particularly, peptide‐coupled AuNCs (Pep‐AuNCs) are emerging as a fascinating class of cluster probes that enable highly tailorable design in their optical, catalytic, targeting, and therapeutic capabilities via peptide engineering. However, a comprehensive review dedicated to decoding the peptide‐directed AuNC design and bioapplication paradigms is still lacking. This review systematically summarizes recent advances in the synthesis, probe design, and bioapplication of Pep‐AuNCs from the perspective of peptide design. The strategies to couple AuNCs with peptides are first discussed, including in situ template synthesis and post‐synthesis modification. Furthermore, we elucidate in detail how peptide sequence, structure, and coupling chemistry dictate the physicochemical and biological properties of AuNCs. We also summarize advanced functions such as specific targeting, stimuli‐responsiveness, and therapeutics that can be rendered from the peptides for broadening the bioapplication potentials of AuNCs. Finally, we discuss the key challenges in their precise synthesis, long‐term stability, and biotransformation study that must be addressed for clinical translation. By linking the peptide programming with the properties and application outcomes of AuNCs, this review aims to offer fundamental insights into the design principles of next‐generation AuNC probes for diagnostic and therapeutic applications.
Liu et al. (Wed,) studied this question.