Rare‐Earth Metal Ions Doped Graphene Quantum Dots for Near‐IR In Vitro/In Vivo/Ex Vivo Imaging Applications
Md. Tanvir Hasan, Roberto González-Rodríguez, Ching‐Wei Lin, Elizabeth A. Campbell, Satvik Vasireddy, Uyanga Tsedev, Angela M. Belcher, Anton V. Naumov
Abstract
Abstract Near‐infrared (NIR) emitting biocompatible nanomaterials are desired in biotechnology as higher penetration depth fluorescence imaging probes. In this work, novel NIR‐emissive Nd 3+ ‐doped or Tm 3+ ‐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 Nd 3+ /Tm 3+ . 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.