A facile and universal ligand exchange strategy enables sequential surface functionalization of quantum dots for high quality in vivo imaging

Fluorescent semiconductor quantum dots (QDs) had the potential to revolutionize biological imaging, but their applications were limited by the difficulties of obtaining biocompatible and high fluorescent-quality QDs due to the difficulty in manipulating surface properties. Here, we explored a facile and effective ligand exchange approach, which enabled sequential surface functionalization and phase transfer of QDs while maintaining QDs fluorescence intensity, size and morphology. Nitrosonium tetrafluoroborate (NOBF 4 ) was employed to substitute for the original organic ligands attached to the QDs surface, stabilizing the QDs in polar and hydrophilic media N , N -dimethylformamide for 60 days without aggregation or precipitation. This method was applicable to a wide range of QDs of different compositions, fluorescence emission wavelengths and sizes. The obtained hydrophilic QDs can subsequently be further functionalized with various capping molecules, which can endow the different surface functionalization of QDs according to the modified molecules employed. Among these, Ag 2 Te QDs after NOBF 4 treatment could undergo sequential surface functionalization, which achieved high-quality in vivo fluorescent imaging. This work offered a versatile ligand exchange strategy for QDs surface functionalization and was a significant step toward controllably engineering the QDs surface properties.