Gold nanomaterials capped with bovine serum albumin for cell and extracellular vesicle imaging

Abstract Bovine serum albumin-capped gold nanoclusters (AuNC@BSA) are ionic, ultra-small, and eco-friendly nanomaterials that exhibit red fluorescence emission. Upon modification, these nanomaterials can serve as imaging probes with multimodal functionality. Owing to their nanoscale properties, AuNC@BSA-based nanomaterials can be readily endocytosed by cells for imaging. With the increasing interest in cell therapy, extracellular vesicles (EVs) have attracted significant attention from researchers; however, effective methods for imaging EVs remain limited. Although several studies have explored imaging strategies for cells and EVs using compounds, nuclear pharmaceuticals, nanoparticles, or genetic constructs, the use of AuNC@BSA-based nanomaterials for labeling EVs and their parental cells has rarely been discussed, with even less attention paid to their multimodal potential. To address this gap, we utilized three types of AuNC@BSA-based derivatives: AuNC@BSA, AuNC@BSA-Gd, and AuNC@BSA-Gd-I. Our findings demonstrate that these derivatives can effectively label both cells and EVs using a simple direct labeling approach, which is particularly notable for EVs, as they typically require more complex labeling procedures. Furthermore, the multimodal potential of labeled cells and EVs was evaluated, revealing their significant capabilities for multimodal imaging. In summary, this study presents an effective strategy for labeling EVs and their parental cells using multimodal nanomaterials. These findings will contribute to accelerating the development of drug delivery systems, cell- and EV-based therapies, and advanced imaging strategies.