Rare-Earth Metal Ions Doped Graphene Quantum Dots for Near-IR In Vitro/In Vivo/Ex Vivo Imaging Applications

Near-infrared (NIR) emitting biocompatible nanomaterials are desired in biotechnology as higher penetration depth fluorescence imaging probes. In this work, novel NIR-emissive Nd3+-doped or Tm3+-doped biocompatible graphene quantum dots (GQDs) are developed via scalable, single-step bottom-up synthesis. Water-soluble Nd-GQDs/Tm-GQDs with average diameters of 5.6-8.2 nm possess crystalline graphene lattice with<1 atomic percent of Nd/Tm and exhibit NIR fluorescence at approximate to 1060/approximate to 925 nm attributed to the intrinsic transitions of Nd3+/Tm3+. High biocompatibility with>80% cell viability at 1 mg mL(-1)for Nd-GQDs and 0.25 mg mL(-1)for Tm-GQDs makes them well-suited for bioimaging. In vitro, both GQD types exhibit efficient internalization with their intracellular emission maximized at 6 h. The pH-dependence of this emission can serve as plethora of diagnostic applications. GQDs enable in vivo NIR imaging in live sedated NCr nude mice with IV administration: their NIR emission maximized at 6 h post-injection is primarily detected in intestine, kidneys, liver, and spleen, however, diminishing to none at 48 h. Ex vivo organ/slice imaging shows significant Tm-GQD fluorescence signatures in the aforementioned organs/slices. This capability of NIR fluorescence imaging in cells, tissues, and real-time detection in live animals makes biocompatible rare-earth metal-doped GQDs an attractive new candidate for in vitro/in vivo/ex vivo theranostics.