Recent advances in biomedical applications of carbon and graphene quantum dots: A review.

The carbon-based nanostructures have led to the development of theranostic nanoplatforms for simultaneous diagnosis and therapy due to their effective cell membrane-penetration ability, low degree of cytotoxicity, excellent pore volume, substantial chemical stability, and reactive surface. In the last few years, extensive efforts were made to design multifunctional nanoplatform strategies based on carbon nanostructures, involving multimodal imaging, controlled drug release capabilities, sensing in vitro, efficient drug loading capacity, and therapy. Carbon and graphene quantum dots (CQDs and GQDs) were the recent entrants, contingently being assessed for drug delivery and bioimaging. With the advancements, these quantum dots have ignited remarkable research interest and are now widely evaluated for diagnosis, bioimaging, sensing, and drug delivery applications. The last decade has witnessed their remarkable electrical, optical, and biocompatible properties since their inception. It is presumed that both of them have high potential as drug carriers and would serve as the next generation of approaches to address numerous unresolved therapeutic challenges. This review examined the recent advances of CQD and GQD based drug delivery applications, challenges, and future perspectives to pave the way for further studies in the future.

A review on synthesis, properties, and biomedical applications of graphene quantum dots (GQDs).

A new type of 0-dimensional carbon-based materials called graphene quantum dots (GQDs) is gaining significant attention as a non-toxic and eco-friendly nanomaterial. GQDs are nanomaterials composed of sp2hybridized carbon domains and functional groups, with their lateral size less than 10 nm. The unique and exceptional physical, chemical, and optical properties arising from the combination of graphene structure and quantum confinement effect due to their nano-size make GQDs more intriguing than other nanomaterials. Particularly, the low toxicity and high solubility derived from the carbon core and abundant edge functional groups offer significant advantages for the application of GQDs in the biomedical field. In this review, we summarize various synthetic methods for preparing GQDs and important factors influencing the physical, chemical, optical, and biological properties of GQDs. Furthermore, the recent application of GQDs in the biomedical field, including biosensor, bioimaging, drug delivery, and therapeutics are discussed. Through this, we provide a brief insight on the tremendous potential of GQDs in biomedical applications and the challenges that need to be overcome in the future.

Transient N-GQDs/PVA nanocomposite thin film for memristor application.

In recent years quantum dot (QDs) based resistive switching devices(memristors) have gained a lot of attention. Here we report the resistive switching behavior of nitrogen-doped graphene quantum dots/Polyvinyl alcohol (N-GQDs/PVA) degradable nanocomposite thin film with different weight percentages (wt.%) of N-GQDs. The memristor device was fabricated by a simple spin coating technique. It was found that 1 wt% N-GQDs/PVA device shows a prominent resistive switching phenomenon with good cyclic stability, high on/off ratio of ~102and retention time of ∼104s. From a detailed experimental study of band structure, we conclude that memristive behavior originates from the space charge controlled conduction (SCLC) mechanism. Further transient property of built memristive device was studied. Within three minutes of being submerged in distilled water, the fabricated memory device was destroyed. This phenomenon facilitates the usage of fabricated memristor devices to develop memory devices for military and security purposes.

Graphene quantum dots on TiO2 nanotubes as a light-assisted peroxidase nanozyme.

Hybrid nanozyme graphene quantum dots (GQDs) deposited TiO2 nanotubes (NTs) on titanium foil (Ti/TiO2 NTs-GQDs) were manufactured by bestowing the hybrid with the advantageous porous morphology, surface valence states, high surface area, and copious active sites. The peroxidase-like activity was investigated through the catalytic oxidation of chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, which can be visualized by the eyes. TiO2 NTs and GQDs comprising oxygen-containing functional groups can oxidize TMB in the presence of H2O2 by mimicking peroxidase enzymes. The peroxidase-mimicking activity of hybrid nanozyme was significantly escalated by introducing light illumination due to the photosensitive features of the hybrid material. The peroxidase-like activity of Ti/TiO2 NTs-GQDs enabled H2O2 determination over the linear range of 7 to 250 µM, with a LOD of 2.1 µM. The satisfying peroxidase activity is possibly due to the unimpeded access of H2O2 to the catalyst's active sites. The porous morphology provides the easy channeling of reactants and products. The periodic structure of the material also gave rise to acceptable reproducibility. Without material functionalization, the Ti/TiO2 NTs-GQDs can be a promising substitute for peroxidases for H2O2 detection.

Boosting Visible-Light Photocatalytic Activity of BiOCl Nanosheets via Synergetic Effect of Oxygen Vacancy Engineering and Graphene Quantum Dots-Sensitization.

In recent years, oxygen vacancy (VO) engineering has become a research hotspot in the field of photocatalysis. Herein, an efficient GQDs/BiOCl-VO heterojunction photocatalyst was fabricated by loading graphene quantum dots (GQDs) onto BiOCl nanosheets containing oxygen vacancies. ESR and XPS characterizations confirmed the formation of oxygen vacancy. Combining experimental analysis and DFT calculations, it was found that oxygen vacancy promoted the chemical adsorption of O2, while GQDs accelerated electron transfer. Benefiting from the synergistic effect of oxygen vacancy, GQDs, and dye sensitization, the as-prepared GQDs/BiOCl-VO sample exhibited improved efficiency for RhB degradation under visible-light irradiation. A 2 wt% GQDs/BiOCl-VO composite effectively degraded 98% of RhB within 20 min. The main active species were proven to be hole (h+) and superoxide radical (·O2-) via ESR analysis and radical trapping experiments. This study provided new insights into the effective removal of organic pollutants from water by combining defect engineering and quantum dot doping techniques in heterojunction catalysts.

Biodistribution of Intravenously Transplanted Mitochondria Conjugated with Graphene Quantum Dots in Diabetic Rats.

Mitochondria transplantation has emerged as a successful therapeutic modality to treat several degenerative diseases. However, the biodistribution of transplanted mitochondria has not been well studied. We investigated the ex-vivo systemic biodistribution and therapeutic efficacy of intravenously transplanted graphene quantum dots (GQDs) conjugated to isolated mitochondria (Mt-GQDs) in diabetic rat tissues. The results revealed that Mt-GQDs facilitate the tracking of transplanted mitochondria without affecting their therapeutic efficacy. It is compelling to note that Mt-GQDs and isolated mitochondria show comparable therapeutic efficacies in decreasing blood glucose levels, oxidative stress, inflammatory gene expressions, and restoration of different mitochondrial functions in pancreatic tissues of diabetic rats. In addition, histological section examination under a fluorescence microscope demonstrated the localization of Mt-GQDs in multiple tissues of diabetic rats. In conclusion, this study indicates that Mt-GQDs provide an effective mitochondrial transplantation tracking modality.

Ratiometric fluorometric determination of sulfide using graphene quantum dots and self-assembled thiolate-capped gold nanoclusters triggered by aluminum.

A ratiometric-based fluorescence emission system was proposed for the determination of sulfide. It consists of blue emissive graphene quantum dots (GQDs) and self-assembled thiolate-protected gold nanoclusters driven by aluminum ion (Al3+@GSH-AuNCs). The two types of fluorophores are combined to form a ratiometric emission probe. The orange emission of Al3+ @GSH-AuNCs at 624 nm was quenched in the presence of sulfide ion owing to the strong affinity between sulfide and Au(I), while the blue GQDs fluorescence at 470 nm remained unaffected. Interestingly, the Al3+@GSH-AuNCs and GQDs were excited under the same excitation wavelength (335 nm). The response ratios (F470/F624) are linearly proportional to the sulfide concentration within the linear range of 0.02-200 µM under the optimal settings, with a limit of detection (S/N = 3) of 0.0064 µM. The proposed emission probe was applied to detect sulfide ions in tap water and wastewater specimens, with recoveries ranging from 95.3% to 103.3% and RSD% ranging from 2.3% to 3.4%, supporting the proposed method's accuracy.

CsPbI3/N-GQDs dual layer phosphor-converted white-LEDs with ultrahigh luminous efficiency and color rendering index.

Phosphor-converted LEDs or pc-LEDs, as a solid-state lighting source, are attractive for next-generation display technologies because of their energy savings, and green environmentally friendly nature. Recently, white LEDs are being produced commercially by coating blue LED (440-470 nm) chips with various yellow-emitting phosphors. However, the LEDs produced by this technique often exhibit high correlated color temperature (CCT) and low color rendering index (CRI) values, due to sufficient red spectral components not being present, and thus aren't suitable for commercial grade white illumination. To circumvent this drawback, our work reports for the first time the use of blue and green-emitting nitrogen-functionalized graphene quantum dots (GQDs) coupled with red-emitting CsPbI3NCs for phosphor-based LED applications. We deployed near-UV to visible excitable red-emitting perovskite CsPbI3nanocrystals which contribute toward the red spectral component, thus greatly improving the CRI of the LEDs. CsPbI3nanocrystals are optically excited by nitrogen-functionalized GQD with blue and green emissions in a remote double-layer phosphor stack technique. This double phosphor layer stacking greatly improves both the CRI and luminous efficiency of radiation (LER), which usually has a trade-off in previously reported phosphor stacks. A CCT of ∼5182 K providing daylight white tonality, with superior CRI (∼90%) and ultrahigh LER (∼250 lumens/watt) are reported, which are significantly higher than the established benchmarks.

Study on the microstructure of the symbiosis of coal-based graphene and coal-based graphene quantum dots: preparation and characterization.

Coal-based graphene sheets (GS) and coal-based graphene quantum dots (GQDs) are usually prepared separately. In this paper, symbiosis of coal-based GS and coal-based GQDs was successfully prepared with our proposed preparation method by using three raw coals with different reflectance (collected from Qinshui coalfield, Shanxi Province) as carbon sources. The results showed that coal-based GS and coal-based GQDs can exist stably in the symbiosis and are distributed in different layers, and the GQDs are freely distributed between layers of GS. The average number of GS (Nave) in the three symbiosis is about 7 and the average interlayer spacing (d002) is about 0.3887 nm. The average diameter of GQDs in the three symbiosis is about 4.255 nm and the averaged002is about 0.230 nm. The averageNaveof the three symbiosis was about 3 and the averaged002is about 0.361 nm. The morphology and crystal parameters of symbiosis is more similar to that of graphene, the elements are only carbon and oxygen. In the prepared symbiosis, the higher the reflectance of raw coal, the smoother the lattice skeleton and the less vortex-layer structure of GS, and the larger the diameter and the denser the six membered ring of GQDs. The C and O functional groups of the prepared symbionts are similar. The higher the reflectance of coal, the higher the content of C-C/C=C. Under ultraviolet light, the prepared products all emit blue, and the higher the reflectance of coal, the higher the ultraviolet absorption, and the stronger the fluorescence intensity.

Structure, morphology and modelling studies of polyvinylalcohol nanocomposites reinforced with nickel oxide nanoparticles and graphene quantum dots.

Nickel oxide (NiO) nanoparticles (NPs) and graphene quantum dots (GQDs) reinforced polyvinyl alcohol (PVA) nanocomposite films were prepared using a solution casting technique. The physicochemical characteristics of PVA/NiO/GQDs (PNG) nanocomposite films were studied using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FESEM). The obtained PNG nanocomposite films showed good mechanical flexibility and improved tensile strength. The influence of nanofiller concentrations on PNG nanocomposite film. The obtained results demonstrate an increase in the activation energy (Ea) up to PNG3 upon increasing the GQDs concentration and thereafter, its decreases. The fundamental interactions of the constituents of PNG nanocomposite film were investigated using density functional theory (DFT). This study on electronic structure reveals that the PVA model indirectly interacts with GQDs through the NiO model. This configuration is favoured in terms of interaction energy (-78 kJ/mol) compared to the one in which PVA interacts directly with the GQDs model.

Synergistic effect of barium titanate nanoparticles and graphene quantum dots on the dielectric properties and conductivity of poly(vinylidenefluoride-co-hexafluoroethylene) films.

PVDF-HFP/BaTiO3/GQDs polymer nanocomposite films with good flexibility and high dielectric constant (ϵ) at low frequency were prepared via solution casting technique. Different compositions of BaTiO3 (non-conducting ceramic nanofiller) and Graphene quantum dots (GQDs) (conducting nanofiller) utilized as co-filler were embedded in poly (vinylidene fluoride-co-hexafluoroethylene) (PVDF-HFP) polymer matrix. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques were employed to characterize the prepared nanocomposite films. The mechanical properties of PVDF-HFP/BaTiO3/GQDs nanocomposite films were also investigated. Dielectric properties of nanocomposite films such as dielectric constant (ϵ), dielectric loss (tanδ) and AC conductivity ( σac ) were also determined as a function of frequency and temperature. Highest ϵ with relatively low tanδ obtained at low frequency for maximum temperature in all polymer nanocomposite films. The σac increases from lower (100 Hz) to higher frequency up to 100 kHz and drops to zero for the further increment of frequency. These results suggest that the PVDF-HFP/BaTiO3/GQDs nanocomposites are the most promising materials for energy storage applications.

Graphene quantum dots: synthesis, properties, and applications to the development of optical and electrochemical sensors for chemical sensing.

GQDs exhibits exceptional electrochemical activity owing to their active edge sites that make them very attractive for biosensing applications. However, their use in the design of new biosensing devices for application to the detection and quantification of toxins, pathogens, and clinical biomarkers has so far not investigated in detail. In this regard, herein we provide a detailed review on various methodologies employed for the synthesis of GQDs, including bottom-up and top-down approaches, with a special focus on their applications in biosensing via fluorescence, photoluminescence, chemiluminescence, electrochemiluminescence, fluorescence resonance energy transfer, and electrochemical techniques. We believe that this review will shed light on the critical issues and widen the applications of GQDs for the design of biosensors with improved analytical response for future applications. HIGHLIGHTS: • Properties of GQDs play a critical role in biosensing applications. • Synthesis of GQDs using top-down and bottom-up approaches is discussed comprehensively. • Overview of advancements in GQD-based sensors over the last decade. • Methods for the design of selective and sensitive GQD-based sensors. • Challenges and opportunities for future GQD-based sensors.

Magnetic graphene quantum dots facilitate closed-tube one-step detection of SARS-CoV-2 with ultra-low field NMR relaxometry.

The rapid and sensitive diagnosis of the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the crucial issues at the outbreak of the ongoing global pandemic that has no valid cure. Here, we propose a SARS-CoV-2 antibody conjugated magnetic graphene quantum dots (GQDs)-based magnetic relaxation switch (MRSw) that specifically recognizes the SARS-CoV-2. The probe of MRSw can be directly mixed with the test sample in a fully sealed vial without sample pretreatment, which largely reduces the testers' risk of infection during the operation. The closed-tube one-step strategy to detect SARS-CoV-2 is developed with home-made ultra-low field nuclear magnetic resonance (ULF NMR) relaxometry working at 118 µT. The magnetic GQDs-based probe shows ultra-high sensitivity in the detection of SARS-CoV-2 due to its high magnetic relaxivity, and the limit of detection is optimized to 248 Particles mL‒1. Meanwhile, the detection time in ULF NMR system is only 2 min, which can significantly improve the efficiency of detection. In short, the magnetic GQDs-based MRSw coupled with ULF NMR can realize a rapid, safe, and sensitive detection of SARS-CoV-2.

PVDF-triggered multicolor fluorine-doped graphene quantum dots for water detection and anti-counterfeiting.

Fluorescent fluorine-doped graphene quantum dots (F-GQDs) have been synthesized via the hydrothermal method using long-chain polymer polyvinylidene fluoride (PVDF) as the precursor. Due to the unique molecular structure of PVDF, a possible synthesis process of F-GQDs has been put forward. F-GQDs have adjustable emission wavelength by simply adjusting the concentration of the solution. As the concentration increases, the emission wavelength of F-GQDs gradually red shifts from 455 nm (blue) to 551 nm (yellow-green). In addition, F-GQDs also exhibit a sensitive fluorescence response to water content in organic solvents, and the ultralow detections limit are 0.056% in ethanol and 0.124% in DMF. Besides, due to strong UV absorption capacity, a photothermal film is fabricated by embedding F-GQDs in PDMS. The temperature of F-GQDs/PDMS polymer film can reach 33.4 oC under simulated sunlight, while the maximum temperature of blank PDMS film only reach 29.4 oC. Based on this phenomenon, a new type of anti-counterfeiting device is designed by combining F-GQDs/PDMS film with temperature change ink.

Developing an Analytical Method Based on Graphene Quantum Dots for Quantification of Deferiprone in Plasma.

In the world of nanotechnology, graphene quantum dots (GQDs) have been considerably employed in numerous optical sensing and bioanalytical applications. Herein, a simple and cost-efficient methodology was developed to the quantification of deferiprone in plasma samples by utilizing the selective interaction of the GQDs and drug in the presence of Fe3+ ions. GQDs were synthesized by a bottom-up technique as an advantageous fluorescent probe. Increasing levels of deferiprone ranging from 5 to 50 mg.L-1, leads to significant fluorescence quenching of GQDs. In addition, the calibration curve was revealed a linear response in this range with a sensitivity of 5 mg.L-1. The method validation was carried out according to the FDA guidelines to confirm the accuracy, precision, stability and selectivity of the developed method. The results show that this green and low-cost fluorescent probe could be used for the analysis of deferiprone.

A dual-mode nanoprobe for the determination of parathion methyl based on graphene quantum dots modified silver nanoparticles.

We developed a highly sensitive and selective method for double-signal analysis (fluorescence and ultraviolet-visible spectrophotometry) of organophosphorus pesticides (OPs), based on reversible quenching of graphene quantum dots (GQDs; fluorophores) with silver nanoparticles (AgNPs; absorbers). We used acetylcholinesterase to catalytically convert acetylthiocholine into thiocholine. In turn, by competitive binding to the AgNPs, the produced thiocholine displaces AgNPs from the GQDs and thus induces fluorescence recovery. However, OP analytes inhibit the activity of acetylcholinesterase and, in so doing, retain the silver-graphene nanoparticle complex and fluorescence quenching. The degree of quenching is proportional to the concentration of OPs; the detection limit is as low as 0.017 µg/L. The ultraviolet-visible absorption of GQDs/AgNPs at 390 nm decreases-because of AgNP aggregation that occurs after desorption from the GQDs-and the absorbance is linearly proportional to the OP concentration. Our system has good selectivity to substances that are commonly present in water and vegetables. We successfully applied our method to OP analysis in water, apple, and carrot samples.

Applications of Graphene Quantum Dots in Biomedical Sensors.

Due to the proliferative cancer rates, cardiovascular diseases, neurodegenerative disorders, autoimmune diseases and a plethora of infections across the globe, it is essential to introduce strategies that can rapidly and specifically detect the ultralow concentrations of relevant biomarkers, pathogens, toxins and pharmaceuticals in biological matrices. Considering these pathophysiologies, various research works have become necessary to fabricate biosensors for their early diagnosis and treatment, using nanomaterials like quantum dots (QDs). These nanomaterials effectively ameliorate the sensor performance with respect to their reproducibility, selectivity as well as sensitivity. In particular, graphene quantum dots (GQDs), which are ideally graphene fragments of nanometer size, constitute discrete features such as acting as attractive fluorophores and excellent electro-catalysts owing to their photo-stability, water-solubility, biocompatibility, non-toxicity and lucrativeness that make them favorable candidates for a wide range of novel biomedical applications. Herein, we reviewed about 300 biomedical studies reported over the last five years which entail the state of art as well as some pioneering ideas with respect to the prominent role of GQDs, especially in the development of optical, electrochemical and photoelectrochemical biosensors. Additionally, we outline the ideal properties of GQDs, their eclectic methods of synthesis, and the general principle behind several biosensing techniques.

Selective fluorometric determination of sulfadiazine based on the growth of silver nanoparticles on graphene quantum dots.

A sensitive fluorometric assay is described for the direct determination of the antibiotic sulfadiazine. Silver nanoparticles placed on graphene quantum dots (Ag NP-GQDs) were synthesized by reduction of AgNO3 with sodium borohydride in the presence of GQDs. The growth of Ag NPs on the surface of the GQDs causes quenching of the blue fluorescence of the GQDs with an emission maximum at 470 nm by surface-enhanced energy transfer. If sulfadiazine is added, it interacts with Ag NPs and fluorescence is restored. Under optimal conditions, the fluorescence increases linearly in the sulfadiazine concentration range of 0.04-22.0 µM. The detection limit is 10 nM with relative standard deviations of 2.3 and 4.2 (at 10 µM of sulfadiazine; for n = 6) for intra- and inter-day assays. Graphical abstractSchematic representation of sulfadiazine determination using Ag NP-GQDs as a fluorescent nanoprobe.

Visible-Light Driven TiO2 Photocatalyst Coated with Graphene Quantum Dots of Tunable Nitrogen Doping.

Nitrogen doped graphene quantum dots (NGQDs) were successfully prepared via a hydrothermal method using citric acid and urea as the carbon and nitrogen precursors, respectively. Due to different post-treatment processes, the obtained NGQDs with different surface modifications exhibited blue light emission, while their visible-light absorption was obviously different. To further understand the roles of nitrogen dopants and N-containing surface groups of NGQDs in the photocatalytic performance, their corresponding composites with TiO2 were utilized to degrade RhB solutions under visible-light irradiation. A series of characterization and photocatalytic performance tests were carried out, which demonstrated that NGQDs play a significant role in enhancing visible-light driven photocatalytic activity and the carrier separation process. The enhanced photocatalytic activity of the NGQDs/TiO2 composites can possibly be attributed to an enhanced visible light absorption ability, and an improved separation and transfer rate of photogenerated carriers.

Computational Analysis on Down-Regulated Images of Macrophage Scavenger Receptor.

BACKGROUND: Thiolated-graphene quantum dots (SH-GQDs) were developed and assessed for an efficient preventive means against atherosclerosis and potential toxicity through computational image analysis and animal model studies. EXPERIMENTS: Zebrafish (wild-type, wt) were used for evaluation of toxicity through the assessment of embryonic mortality, malformation and ROS generation. The amounts of SH-GQDs uptaken by mouse macrophage cells (Raw264.7) were analyzed using a flow cytometer. For the time-dependent cellular uptake study, Raw264.7 cells were treated with SH-GQDs (200 µg/ml) at specific time intervals (0.5, 1, 2, 5, 10 and 24 h). The efficacy of SH-GQDs on DiO-oxLDL efflux by Raw264.7 cells was evaluated (DiO, 3,3'-dioctadecyl-oxacarbocyanine) based on the percentage of positive cells containing DiO-oxLDL. TEER of human primary umbilical vein endothelial cells (hUVECs) were examined to assess the barrier function of the cell layers upon being treated with oxLDL. RESULTS: SH-GQDs significantly enhanced the efflux of oxLDL and down-regulated macrophage scavenger receptor (MSR) in Raw264.7. The ROS levels stimulated by oxidative stress were alleviated by SH-GQDs. oxLDL (10 µg/ml) significantly impaired the barrier function (TEER) of adherence junctions, which was recovered by SH-GQDs (10 µg/ml) (oxLDL: 67.2 ± 2.2 Ω-cm2 for 24 h; SH-GQDs: 114.6 ± 8.5 Ω-cm2 for 24 h). The mortality rate (46% for 1 mg/ml) of the zebra fish increased, as the concentrations and exposure duration of SH-GQDs increased. SH-GQDs exerted negligible side effects. CONCLUSION: SH-GQDs have target specificity to macrophage scavenger receptor (MSR) and efficiently recovered the ROS levels and TEER. SH-GQDs did not induce endothelial cell layer disruption nor affected zebrafish larvae survival.