Peptide and Drug‐Protected Gold Nanoclusters as Promising Biomaterials: Synthesis, Properties, and Applications

ABSTRACT Peptide‐ and drug‐protected gold nanoclusters (Au NCs) with atomic precision have attracted research attention in the last few years owing to their ultrasmall size (<2 nm), well‐defined structures, tunable photoluminescence from the visible to near‐infrared range, water solubility, and good biocompatibility. These features, combined with low toxicity and efficient renal clearance, make such Au NCs promising candidates for biomedical use, including diagnosis, therapy, and theranostic. The incorporation of peptides or drugs into Au NCs enhances the stability, targeting specificity, cellular uptake, and prolonged circulation, enabling precise modulation of biological responses. Despite notable advances in achieving atomic precision employing complex ligands such as peptides or drugs, the synthetic methods of this new class of NCs remain a challenge. Careful control of molar ratio (Au: peptide/drug), reducing agent, temperature, and reaction time is required, because these factors directly influence the cluster size, optical properties, and in vivo performance. In this review, we highlight different synthetic approaches of atomically precise peptide‐ and drug‐protected Au NCs, emphasizing the role of rational ligand design and reaction conditions, as well as the challenges associated with structural determination. We further discuss the optical and photoluminescence properties of peptide‐protected Au NCs—the mostly explored features for biomedical applications. Finally, we conclude by outlining the current challenges, opportunities for scale‐up synthesis, and future design perspectives for these emerging nanomaterials.