【introduction】

Graphene quantum dots (GQDs) are carbon-based nanoparticles with excellent chemical, physical, and biological properties that make them stand out in a wide range of nanomedicine applications. The unique electronic structure of GQDs gives these nanomaterials powerful and tunable photoluminescence (PL) functions for fluorescent bioimaging and biosensing; small molecule drug delivery of aromatic compounds with high loading capacity; absorption of incident radiation Capabilities, cancer killing technology for photothermal and photodynamic therapy.

[Achievement Profile]

Recently, led by Professor Zhang Miqin‘s team (corresponding author) at the University of Washington , he first reviewed the physical and chemical properties, optical properties, electronic properties, magnetic properties and biological properties of GQDs, discussed the research progress of GQDs in recent years, and introduced the GQD synthesis methods Research advances; classification of these methods based on techniques that rely on top-down or bottom-up processes. Later, the applications of GQDs will be discussed, including optical imaging and magnetic bioimaging, in vivo and in vitro biosensing, and treatment methods through drug delivery, gene delivery, and photodynamic therapy (PDT). The current limitations and future directions of GQD research are also analyzed in depth. Related results were published on Adv. Mater. Under the title " Graphene Quantum Dots and Their Applications in Bioimaging, Biosensing, and Therapy " .

[Picture and text guide]

Figure 1 Research progress in the synthesis, physical properties, and applications of graphene quantum dots (GQD) in biological systems

Figure 2 Schematic diagram of the structural differences between graphene, graphene oxide, graphene quantum dots, and carbon quantum dots

Figure 3 calculates the effect of size and edge conformation on the band gap of GQDs through a theoretical model

a) Structure of GQDs of different sizes and edge configurations. The labels "AM" and "ZZ" refer to the edge type, and the integer indicates the number of aromatic rings.

b) The band gap varies with the lateral size and edge type. The following letters indicate the modeling methods used: Green‘s function and shielded Coulomb interaction (GW) and local density approximation (LDA).

Fig. 4 PL spectrum of GQDs changes with doping properties and degree

a) Photographs of GQDs and nitrogen-doped GQDs (NGQDs). The number after the NGQD label indicates the irradiation time in min under NH ₃ atmosphere.

b) PL spectrum of NGQDs synthesized under NH ₃ atmosphere. As nitrogen atoms are incorporated into GQDs, NGQDs undergo blue shift.

c) PL spectra of aromatic amine-functionalized GQDs. N _ar / N represents the ratio of aromatic amines to total amines. As the aromatic amine functionalization increased, a noticeable red shift appeared in the spectrum.

d) UV-vis (black) and PL spectrum (color) of the original GQDs and e) boron-doped GQDs at different excitation wavelengths. When boron is incorporated into the structure, a slight red shift occurs.

FIG 5 Evaluation GQD S biocompatible

a) Evaluation of cell metabolic activity of A549 cells after exposure to three different concentrations of GQDs.

b) Four weeks after intravenous injection of GQDs, histological evaluation of important organs in rats.

c) In the dark, cell viability can be changed by reacting GQDs and GQDs at different concentrations with the following substances: phenylhydrazine (PH), benzoic anhydride (BA), and 2-bromo-1-acetophenone (BrPE).

d) Under irradiation, the cell viability can be changed by reacting GQDs and GQDs at different concentrations with the following substances: phenylhydrazine (PH), benzoic anhydride (BA) and 2-bromo-1-acetophenone (BrPE).

Figure 6 Schematic diagram of the latest progress of GQD synthesis from top-down and bottom-up methods

Figure 7 Characterization of GQDs synthesized by liquid phase stripping

a) Schematic diagram of liquid phase stripping and GQDs synthesis mechanism.

b) PL spectra of HD-GQDs and c) LD-GQDs at different excitation wavelengths.

Figure 8 Microwave synthesis of GQDs

a) Schematic illustration of microwave synthesis of N-GQD and b) NS-GQD, showing the functionalization of GQDs with amine and sulfur functional groups.

Figure 9 Nitrogen-doped GQDs for cell and tissue imaging

a) PL emission spectra of single-photon fluorescence (OPF) and two-photon fluorescence (TPF).

b, c) b) bright field and c) fluorescence image of HeLa cells under 800 nm excitation (scale bar = 10 μm).

d) Schematic of two-photon fluorescence imaging (TPFI) device using tissue phantoms of different thicknesses.

e) N-GQDs penetration depth of TPFI and single-photon fluorescence imaging (OPFI) in tissue phantoms (scale bar = 100 μm).

Figure 10 Nitrogen and boron doped GQDs for NIR-II bioimaging

a) Transmission electron microscope image showing monodisperse particles with a diameter of 5 nm. The upper-right inset shows the lattice fringes indicating graphene, while the lower-left inset is a photograph of GQDs in solution, showing their excellent solubility.

b) When excited by a 808 nm laser source, shows the PL spectrum of NB-GQDs emitted by NIR-II. The inset shows optical and PL images of NB-GQDs in aqueous solution.

c) To evaluate the cytotoxicity of NB-GQDs in vitro by evaluating the viability of SF763, 4T1 and B16F10 cells after 72 hours of incubation with NB-GQDs. Statistical analysis was performed using students‘ two-tailed t-test (** p <0.01, *** p <0.001).

d) In vivo NIR-II imaging of live mice. The top left panel is a picture of nude mice, and the top subsequent panel depicts PL images of mice injected with phosphate buffered saline (PBS) but without any contrast agent. The second and third rows of images depict the time course of PL images after intravenous injection of NB-GQDs. The image in the bottom row highlights the PL in the blood vessel.

Figure 11 In vivo T1-weighted MR images of abdominal cross sections of mice treated with boron-doped GQDs

In vivo T1-weighted MR images of abdominal cross-sections of mice were treated with boron-doped GQDs, and dynamic time-resolved MR imaging was obtained at various time points after intravenous injection. The arrows indicate various organs: heart (H), liver (L), kidney (K), spleen (Sp), and stomach (St). 68 minutes after dosing, the heart and stomach showed maximum contrast.

Figure 12 DNPTYR-GQD-based H2S sensing PL on nanoprobe

a) Schematic of the synthesis and PL quenching mechanism of GQD-DNPTYR.

One hour after b) GQD-DNPTYR treatment (second from left), H ₂ S is present 25 minutes (third from left) Confocal images and not incubated in GQD-DNPTYR in MCF-7 cells (leftmost). There are H ₂ S and PMA (far right). GQD-DNPTYR emits green fluorescence and NucBlue emits blue fluorescence. Scale bar = 10 μm.

Figure 13 Schematic diagram of paper insertion into a GQD-based sensor

a) Examples of phenolic compounds that can (yellow) and cannot (red) quench GQDs.

b) Schematic diagram of the device used to illuminate the pattern.

c) The circuit of the UV LED connected to the USB port.

d) Schematic diagram of nitrocellulose tape containing embedded GQDs in a circular area separated by printing wax.

e) An image of the sensor system in use. The screen shows the sample read through the fluorescent spots detected by the camera.

f) Schematic representation of typical Yes / No results.

Figure 14 Therapeutic application of GQDs

The chemotherapeutic drugs can be loaded onto the basal plane of GQDs through π orbit stacking. Doxorubicin (DOX) is a typical small molecule chemotherapeutic drug (top left). GQDs can be positively charged by binding edge groups to cationic peptides, forming complexes with negatively charged DNA or RNA for gene therapy (top right). GQDs can be used as photosensitizers to generate active oxygen when irradiated at a specific wavelength (bottom). GQDs have proven to be effective photosensitizers in photodynamic therapy.

Figure 15 GQDs delivered by MTX

a) Schematic diagram of N-GQD synthesis by hydrothermal method, formation of MTX- (N-GQD) complex and intracellular release.

b) In vitro cytotoxicity of MTX- (N-GQDs) was assessed after 48 hours of culture. MCF-7 cells were exposed to different concentrations of free MTX (dark bars) and MTX- (N-GQDs) (light bars). Compared with MTX- (N-GQDs), the statistical significance of MTX viability is represented by * and **, respectively, p <0.05 and p <0.01.

c) Cytotoxicity assessment of N-GQDs without MTX.

Figure 16 GQDs of PDT

a) After irradiation with a 500 W xenon lamp, the light stability of GQDs, Ppix, and CdTe and the change over time in absorbance at 470 nm were measured.

b, c) b) brightfield and c) red fluorescence images after subcutaneous injection of GQDs in mice.

d) Volume of tumors in three groups over time (n = 5 in each group). P <0.05 for each group. PDT: GQD + irradiation, C1: GQD only, C2: light irradiation only).

e) Photographs of mice after various treatments (integer numbers after treatment labels represent days after first treatment).

[ Summary ]

Recent advances in GQD research indicate that GQD has the potential as a new platform for biotechnology and nanomedicine. The method of doping and functionalizing GQDs was studied by a new synthetic method, and the effects of optical, electronic, magnetic and biological properties were used to apply GQDs to the medical field. In order to optimize the physical and chemical properties of GQDs so that they have the necessary characteristics for specific applications, new experimental methods have been developed. In addition, various studies have focused on the development of safe and simple "one-pot" synthesis methods, using some simple precursor molecules and off-the-shelf equipment, such as domestic microwave ovens. These achievements show GQDs as a convenient system for nanomedicine.

Literature link: Graphene Quantum Dots and Their Applications in Bioimaging, Biosensing, and Therapy (Adv. Mater., 2019, DOI: 10.1002 / adma.201904362)

Source of information: material cattle