Dual-Mode Fluorescence/Ultrasound Imaging with Biocompatible Metal-Doped Graphene Quantum Dots

Sonography offers many advantages over standard methods of diagnostic imaging due to its non-invasiveness, substantial tissue penetration depth, and low cost. The benefits of ultrasound imaging call for the development of ultrasound-trackable drug delivery vehicles that can address a variety of therapeutic targets. One disadvantage of the technique is the lack of high-precision imaging, which can be circumvented by complementing ultrasound contrast agents with visible and, especially, near-infrared (NIR) fluorophores. In this work, we, for the first time, develop a variety of lightly metal-doped (iron oxide, silver, thulium, neodymium, cerium oxide, cerium chloride, and molybdenum disulfide) nitrogen-containing graphene quantum dots (NGQDs) that demonstrate high-contrast properties in the ultrasound brightness mode and exhibit visible and/or near-infrared fluorescence imaging capabilities. NGQDs synthesized from glucosamine precursors with only a few percent metal doping do not introduce additional toxicity in vitro, yielding over 80% cell viability up to 2 mg/mL doses. Their small (