Aqueous synthesis of PEGylated Ag₂S quantum dots and their in vivo tumor targeting behavior

With significantly decreased light scattering and tissue autofluorescence, fluorescence imaging in the second near infrared (NIR-II, 1000-1700 nm) region has been heavily explored in biomedical field recently. Silver sulfide quantum dots (Ag₂S QDs) with unique optical properties were one of the most classic NIR-II imaging probes. However, the Ag₂S QDs for in vivo purpose were mainly obtain by oil phase-based high-temperature route at present. Here, we proposed a mild aqueous route to prepare NIR-II emissive Ag₂S QDs for in vivo tumor imaging. Original Ag₂S QDs was obtained by mixing sodium sulfide and silver nitrate in a thiol-terminated polyethylene glycol (mPEG-SH) solution. Treating the original Ag₂S QDs with extra mPEG-SH ligands produced highly PEGyalted Ag₂S QDs. These re-PEGylated Ag₂S QDs exhibited much better blood circulation and tumor accumulation in vivo comparing with the original ones, which can serve as excellent tumor imaging probes. The whole-body blood vessel imaging of living mice was achieved with high resolution, the bio-distribution of these QDs were studied by NIR-II imaging as well. This work also highlighted the importance of ligand density for tumor targeting.