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.

Biological nanoscale fluorescent probes: From structure and performance to bioimaging

“…Some researchers are interested in the development of carbon points emitting red fluorescence and their application in near-infrared biological imaging [95][96][97]. Li et al attached electron acceptor groups (rich in sulfoxide/carbonyl groups) to the outer layer and edges of the CDs.…”

Graphene Quantum Dots (GQDs) for Bioimaging and Drug Delivery Applications: A Review

“… The NIR fluorescence of GQDs showed excellent performance due to their remarkable attributes such as the deep penetration depth, nonblinking fluorescence emission, facile spatiotemporal control, good water solubility, and biocompatibility. − Feng et al, for the first time, reported the two-photon (TP) behavior of GQDs with an NIR emission at 660 nm upon excitation with 810 nm femtosecond pulses having a cross-section of 25.12 GM . The developed nanoprobe using CoOOH-NIR GQDs (N-GQDs) was successfully applied to detect ascorbic acid (AA) in living cells as well as deep-tissue imaging .…”

Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications

“…In comparison, GQDs with diameters ranging from 0.89 to 1.80 nm emit fluorescence covering the entire visible light spectrum range (400–770 nm) [ 246 ]. The NIR fluorescence of GQDs showed excellent performance due to their remarkable attributes such as deep penetration depth, unblinking fluorescence emission, easy spatiotemporal control, good water solubility, and biocompatibility [ 247 , 248 ].…”