Aqueous synthesis of Ag and Mn co-doped In₂S₃/ZnS quantum dots with tunable emission for dual-modal targeted imaging

Here, we present the microwave-assisted synthesis of In₂S₃/ZnS core/shell quantum dots (QDs) co-doped with Ag⁺ and Mn²⁺ (referred to as AgMn:In₂S₃/ZnS). Ag⁺ altered the optical properties of the host QDs, whereas the spin magnetic moment (S =5/2) of Mn²⁺ efficiently induced the longitudinal relaxation of water protons. To the best of our knowledge, this is the first report of the aqueous synthesis of color-tunable AgMn:In₂S₃/ZnS core/shell QDs with magnetic properties. The synthetic procedure is rapid, facile, reproducible, and scalable. The obtained QDs offered a satisfactory quantum yield (45%), high longitudinal relaxivity (6.84s^-1 mM^-1), and robust photostability. In addition, they exhibited excellent stability over a wide pH range (5-12) and high ionic strength (0.15-2.0M NaCl). As seen by confocal microscopy and magnetic resonance imaging, AgMn:In₂S₃/ZnS conjugated to hyaluronic acid (referred to as AgMn:In₂S₃/ZnS@HA) efficiently and specifically targeted cluster determinant 44, a receptor overexpressed on cancer cells. Moreover, AgMn:In₂S₃/ZnS@HA showed negligible cytotoxicity in vitro and in vivo, rendering it a promising diagnostic probe for dual-modal imaging in clinical applications. Statement of Significance: In this manuscript, we reported a facial and rapid method to prepare In₂S₃/ZnS core/shell quantum dots (QDs) co-doped with Ag⁺ and Mn²⁺ (referred to as AgMn:In₂S₃/ZnS). Ag⁺ dopants were used to alter the optical properties of the In₂S₃ host, whereas Mn²⁺ co-dopants with their unpaired electrons provided paramagnetic properties. The emission wavelength of the core/shell QDs could be tuned from 550 to 743nm with a maximum PL quantum yield of 45%. The resulting core/shell QDs also maintained a stable emission in aqueous solution at broad ranges of pH (5-12) and ionic strength (0.15-2.0M NaCl), as well as a high photostability under continuous irradiation. In vivo cytotoxicity experiments showed that up to 500μg/mL AgMn:In₂S₃/ZnS@HA did not cause obvious toxicity to zebrafish embryos. In vitro targeted cell luminescence and magnetic resonance imaging showed that AgMn:In₂S₃/ZnS conjugated to hyaluronic acid was selectively and efficiently internalized in CD44-expressing tumor cells, confirming that the resultant QDs could function as dual-modal imaging probes for accurate diagnosis.