Metal-Doped Graphene Quantum Dots as Ultrasound Contrast Agents

Sonography offers many advantages over standard methods of therapeutic imaging due to its non-invasiveness, deep penetration, high spatial and temporal resolution, low cost, and portability. The benefits of ultrasound imaging call for the development of ultrasound-tracked drug delivery vehicles that can serve a variety of therapeutics. In this work, we have for the first time developed a variety of metal-doped graphene quantum dots (GQDs) that demonstrate high-contrast properties in ultrasound brightness mode. The successful imaging enhancement was observed in tissue phantom and animal tissue. These GQDs with only a few percent metal doping possess high ~1 mg/mL biocompatibility, small (<10 nm) sufficient for effective cell internalization size, and a variety of oxygen-containing surface functional groups rendering them water-soluble and allowing for potential attachment of therapeutics. They also provide additional imaging modalities via their intrinsic visible and/or near-infrared fluorescence that has been observed in vitro in HEK-293 cells. A combination of non-invasive ultrasound tracking modalities with capabilities of fluorescence imaging and drug attachment makes metal-doped GQDs a viable therapeutic vehicle for a variety of complex conditions.