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

Abstract 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 ≈1060/≈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.