Engineering ultrasmall gold nanoclusters: tailored optical modulation for phototherapeutic and multimodal biomedical applications

Ultrasmall gold nanoclusters (Au NCs) with core sizes below 2 nm exhibit distinctive physicochemical properties and hold remarkable promise in a variety of biomedical applications. Through precise synthesis and surface engineering, Au NCs can be endowed with high quantum yields, excellent stability, and favorable biocompatibility. Recent studies have demonstrated the versatility of Au NCs in imaging modalities-ranging from fluorescence and Raman to photoacoustics-as well as in light-driven therapeutics such as photodynamic therapy (PDT) and photothermal therapy (PTT). This review provides an overview of Au NC design strategies, highlighting ligand-assisted synthesis and supramolecular self-assembly for optimizing optical features and biological performance. Representative biomedical applications in optical imaging, biosensing, and phototherapy are summarized to illustrate the multifaceted benefits of Au NCs in disease diagnosis and treatment. Finally, challenges related to large-scale production, long-term biosafety, and clinical translation are discussed, along with future perspectives on leveraging Au NCs for next-generation theranostic platforms.