Precise Blood Glucose Sensing by Nitrogen-Doped Graphene Quantum Dots for Tight Control of Diabetes

Mousavi, Seyyed Mojtaba; Hashemi, Seyyed Alireza; Gholami, Ahmad; Mazraedoost, Sargol; Chiang, Wei-Hung; Arjmand, Omid; Omidifar, Navid; Babapoor, Aziz

doi:https://doi.org/10.1155/2021/5580203

Journal of Sensors

On this page

Abstract Introduction Conclusion Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2021 | Article ID 5580203 | https://doi.org/10.1155/2021/5580203

Precise Blood Glucose Sensing by Nitrogen-Doped Graphene Quantum Dots for Tight Control of Diabetes

Seyyed Mojtaba Mousavi,¹Seyyed Alireza Hashemi,²Ahmad Gholami,³Sargol Mazraedoost,³Wei-Hung Chiang,¹Omid Arjmand,⁴Navid Omidifar,^4,5and Aziz Babapoor⁶

Academic Editor: J.G. Manjunatha

Received21 Feb 2021

Accepted24 Jun 2021

Published17 Jul 2021

Abstract

Graphene quantum dots (GQD) are novel fluorescent carbon nanomaterials based on a graphite structure. Thanks to extraordinary properties such as high surface area and enhanced prevalent optical properties, they have received more interest for special applications. Glucose sensing is a critical factor for the diagnosis, and treatment of diabetes plays an important role and could contribute to the monitoring of diabetes and other related parameters, which has been effectively underscoring the health society. Detecting glucose has been cultivated through different systems, for example, electrochemical or optical techniques. Novel transducers made with GQD that fluorescent coordinate methods have considered the improvement of cutting-edge glucose sensors with prevalent affectability and accommodation. Currently, detection of glucose by nitrogen-doped GQD frameworks concerning the determined objectives has been considerably considered. Here, we explored the properties of fluorescent nitrogen-doped GQD as an excellent and effective index that significantly could promote nitrogen-doped GQDs and make them an appropriate candidate for detecting glucose.

1. Introduction

An extraordinary investigation among building up the graphene and its subordinates has recently been animated for upgraded clinical advances. As a two-dimensional honeycomb organizer comprising sp2 hybridized carbon (sp2 C) iotas, graphene has shown many superior synthetic and physical properties because of this specific two-dimensional layered structure [1]. Diabetes is a metabolic disease, revealed by blood glucose maintenances and reasons with long haul harm and breakdown of different organs, just like the eyes, kidney, heart, and veins [2]. The initial and delicate disclosure of unpredictable glucose levels interior the blood is exceptionally fundamental for veritable treatment to decrease different thriving issues [2, 3]. Diabetes mellitus is a ceaseless condition that influences more than 420 million individuals worldwide and is the primary source of death [4]. Diabetic individuals have fundamental degrees of blood glucose in controlling glycemic levels and decreasing the indications of the illness. Glucose sensors have been utilized for diabetes for over 50 years, given that Clark and Ann Lyons developed the principal glucose catalyst in 1962. Electrochemical sensors have improved the indispensable innovation for estimating glucose levels with the most broadly accessible strategies for amperometric detection. In expansion, distinguishing glucose in the blood is a broad research component [5–8]. The improvement of new fluorescent nanomaterials opened a weak outlook so that the level of blood glucose be controlled at average level as it is expected. Such sensors incorporate nanoparticles containing carbon dabs, quantum spots, graphene quantum dabs, gold, silver, and upconversion [9]. A modest bunch of methodologies has been utilized to form the glucose biosensors subordinate to glucose oxidase protein. In any case, the immobilization of a protein on the cathode surface may be an especially testing task, and it is thoroughly influenced by temperature, pH, and clamminess, which causes down and out unfaltering quality [10, 11]. Along these lines, nonenzymatic glucose sensors are supported and have been widely investigated and considered [12]. Graphene as a promised material, depending on its excellent features in a wide range of scientific fields, such as photonic gadgets, low force hardware, electrochemical vitality and capacity frameworks, impetuses, organic and synthetic sensors, bioimaging, and tissue engineering, is widely utilized [13, 14]. Graphene could easily modify various surfaces as used, making it an excellent material with a few side effects [15, 16]. Doping nitrogen on GQDs was first introduced in 2012, and from that point onward, more endeavors have been made for investigating various techniques for DFCDs with different heteroatoms [17–19]. Yet, before treating individuals with diabetes, the precise, quick, and stable discovery of glucose level is the most extreme genuine errand for the individuals who will probably get individuals with diabetes [20]. Hence, nonenzymatic glucose biosensors have been grown as of late to the clinical network. Subsequently, these nonenzymatic glucose biosensors have revealed much prevalent adequacy and affectability that other enzymatic sensors and have been made a bundle during the previous decades, and entering GQDs to this sensor have caused a colossal adjust in glucose revelation [16, 21–24].

2. GQDs and Nitrogen-Doped GQD Preparation

The GQDs are mainly composed of glucose pyrolysis, as illustrated in (Figure 1). Generally, GQDs are prepared in two ways called the bottom-up way and the top-down way. Although, the top-down method comes with several disadvantages, including more challenging size distribution control, lower yield, critical synthesis environment, and special equipment requirements. On the other side, the bottom-up strategy, also called thermal treatment and carbonizing some unique, organic materials, generally allows specific size and morphology control over the distribution of products. However, the used organic precursors need complicated synthesis procedures and are difficult to obtain [25–28].

Recently, Liu et al. [29] reported GQDs prepared from hexaperihexabenzocoronene pyrolysis. Furthermore, GQDs were designed as starting materials from citric acid and glutathione, too [29, 30]. In another study, Wu et al. used a simple one-step synthesis of GQSs by pyrolysis of L-glutamic acid in a heating mantle [31]. Wang and Zhou [32] also reported the Gram-scale synthesis of functionalized GQDs using pyrene through a facile molecular fusion route. Also, fluorescent nitrogen-doped graphene quantum dots were developed using the bottom-up method via one-step pyrolysis of citric acid and tris (hydroxymethyl) aminomethane [33, 34].

Numerous groups have attempted to make GQD by emerging carbon materials and oxidizing them with acidic compounds in the top-down route technique. Also, solvothermal and hydrothermal treatments were used for GQDs synthesis [35, 36]. The electrochemical route might provide some benefits as essential parameters, including easy manipulation, lower cost, and more ecological. Recently, graphene film formed by filtration as cyclic voltammetry (CV) scan electrode in a phosphate buffer solution to build uniform diameter GQD at 3–5 nm by Li et al. [37]. Bao et al. [38] also used electrochemical etching carbon fibers for GQD preparations at a stable probable for further hours in acetonitrile explanation [38]. In another report by Shinde et al., multiwall carbon nanotubes were electrochemically transformed on a one two-step process for preparing GQD. Despite this, this electrochemical method involves a graphene-like electrode, and hence, it is not proper for the production of GQD on a large scale. Therefore, to develop an extensive scale method for GQDs preparation from GO, a group of researchers introduced an economical and novel route of electrochemical modifications. Given that the reported GQD yield was above 65.5%. Hence, this method as a controllable and straightforward way for different scales of industrial levels could provide excellent performance. These GQDs provided different emission colors and sizes with noticeable peroxidase-like activity, suggesting their high potential in biosensors applications [24, 33]. Figure 2 illustrates a schematic of other methods of GQD preparation.

During the past years, doping carbon materials with nitrogen have received more attention than reported [40]. Currently, nitrogen-doped fluorescent carbon nanomaterials are widely utilized as the promoted materials in many fields, mainly in biomedical areas such as biosensing and bioimaging specific compounds, photocatalysis, electrocatalysis, and photovoltaics [41, 42]. Here, we describe some of the biomedical applications of nitrogen-doped GQDs.

3. Biosensing and Bioimaging Activities of Nitrogen-Doped GQDs

Bioimaging and biosensing as two essential applications of nitrogen-doped fluorescent carbon dots to quantum dots have been put forward and considered. Many factors are required for nitrogen-doped fluorescent carbon dots or quantum dots so that they could be used as biosensors or bioimaging agents, such as a suitable PL intensity and an under approximately seven pH value. Additionally, their low toxicity as a key and effective parameter could contribute to achieving the best clinical efficiency as it is involved different cell types at particular concentrations with subject to the determined and targeted environment. It was worth mentioning to note that the nitrogen-doped quantum dots showed no apparent toxicity on 1 mg/mL concentration as prepared (Figure 3). As an additional sample, the nitrogen-GQDs are formulated through pyrolysis of ethylene diamine tetraacetic acid (EDTA), indicating lower cytotoxicity, allowing the cells to maintain their feasibility even below 140 μg/mL attentiveness [32, 43, 44]. The results also revealed that nitrogen-quantum dots constructed from milk presented curiously lower toxicity than one made from EDTA [45] (Figure 4(a), solid lines).

(a)

(b)

(a)

(b)

(c)

(d)

E-GQD UV-vis absorption spectrum showed the preoccupation band at about 340 nm (Figure 4(a), dash lines). The RAW 264.7 cells are discovered due to the strong fluorescence signal of E-GQDs (Figures 4(b)–4(d)). Additional studies confirmed that the doping quantum and carbon dots with nitrogen would grant more robust fluorescence release than the nondoped ones intended for bioimaging fields [45]. Nitrogen codoping with N and additional components have been utilized in cell imaging as they showed a few unpredictable behaviors in their optical possessions [42, 46].

It is concluded that the nitrogen-doped GQDs indicated a pH, H₂O₂ concentration, and temperature-dependent catalytic activity with peroxiding behavior, which is similar to the HRP. In kinetic analysis, it was also revealed that nitrogen-doped GQDs showed noticeable catalytic activity. Nitrogen-doped GQDs are unique and natural enzyme mimetic, with various benefits over the natural bulk enzymes, including delicate stability, economical and low cost, higher surface area ratio, and high potential to bond through p-p interactions. Finally, using nitrogen-doped GQDs with catalytic activities and peroxidase-like behavior is a convenient and sensitive quantitative and colorimetric agent for H₂O₂ and glucose detection. Therefore, this assay was employed in diluted serum and fruit juice for glucose detection. The experimental tests (Figure 5) demonstrated nitrogen-doped GQDs as great nominees for medical diagnostics and other biomedical applications [47].

(a)

(b)

(c)

(d)

Figure 5

(a) UV–vis absorption spectra and (b) direct calibration plots for the H₂O₂ area utilizing N-GQD peroxidase-like catalytic reaction. (c) UV–vis digestion spectra and (d) coordinate calibration plots for the glucose area utilizing glucose oxidase (GOx) and N-GQDs (inset: dose-response twists for H₂O₂ revelation utilizing N-GQD peroxidase-like catalytic reaction (a) and glucose disclosure utilizing GOx and N-GQDs (c); photographs for colorimetric revelation for H₂O₂ (b) and glucose (d), independently). Test conditions for H₂O₂ and glucose area: 500 mL N-GQDs 320 mg/mL, 200 mL TMB 5 mM, 5 mL GOx 40 mg/mL, and different volumes of H₂O₂ 50 mM or glucose 1 mM in 200 mL H₃PO₄–Na₂HPO₄ 100 mM buffer course of action (pH 3.0) at 35°C. Each point is an ordinary of three dynamic estimations. Bumble bars talk to the commonplace botch decided from three dynamic estimations [47].

4. The Selectivity of the Organized GQD-PBS Glucose Sensor

Glucose revelation and identification have a significant portion in food businesses and pharmaceutical zones, and more vitally, glucose identifying is outstandingly fundamental for curing diabetes. Diabetes is considered as long-term hyperglycemia, and so the glucose area is essential for controlling the illness. The detection of glucose using the electrochemical approach may be put forward as a standard procedure for recognizing blood glucose resistance to insulin. In any case, the blood test-taking preparation may be considered a poorly designed way for testing; conjointly, the risk of infection could be a stressful issue for numerous individuals. In this manner, characteristic working frameworks, being noninvasive or minor obtrusive fluorescent location innovations, have innumerable interfaces [48]. Fluorescent detecting provides different benefits. In quintessence, being exceedingly touchy more than other detecting strategies, noninvasive or minor obtrusive, the life expectancy of fluorescence escalated is utilizable, and the fluorescent reverberation vitality approach can be functionalized as well. The root of glucose fluorescent location is unexpected on glucose signals being changed over to a connected fluorescence flag.

For this aim, a glucose-recognized biomolecule with a flag finder and transducer is required [49]. Nanomaterials with fluorescence movement are perfect flag transducers for connecting glucose signals into fluorescence signals, particularly in top escalated and move for a fluorescent lifetime. In nanobiosensing systems, fluorescence resonation essentialness trade (Worry) is a tried and true and redress informative technique. Nanomaterials have a high performance for finding glucose in numerous interior stages of the body or target cells. Biomolecules are exceptionally profoundly boosted in their organic action by physical adsorption or conjugation on nanomaterials for higher biological applications.

Nanobiosensing of glucose by fluorescent materials depends on the taking after instrument, as the arrangement and competitive official of glucose, at that point release of fluorescent color, which impacts the fluorescent lifetime. In other measures, catalytic oxidation responses such as gluconic corrosive (pH) or hydrogen peroxide are utilized in glucose, making the fluorescent alter. A few glucose oxidation forms contain ATP as adenosine triphosphate and ADP as adenosine diphosphate [9]. As of late, GQDs were organized utilizing glucose carbonization handle as a required course. After that, these GQDs were functionalized using phenylboronic destructive receptors as identifying administrators for nonenzymatic glucose sensors. The photoluminescence sensor was joined, comprising phenylboronic salt, and utilized GQDs for glucose particle revelation. PBS functionalized graphene quantum spot-based sensor recognized glucose interior to reach 4–40 mM, differentiating 72–720 mg/dL. This fluorescent sensor includes a coordinate consolidate method and can be taken care of for an all-encompassing time allotment for zone applications. The utilized sensor appeared a prompt response to glucose through a relationship coefficient of 0.97 and a moo disclosure controls around 3.0 mM (Figure 6) [33].

Glucose detection and sensing have a crucial role in food industries and pharmaceutical fields, and more importantly, glucose sensing is critical for curing diabetes. Diabetes is considered as long-term hyperglycemia, and therefore, glucose detection is necessary for controlling the disease. Electrochemical glucose sensing is a standard method for patience in terms of a blood glucose meter. However, the blood sample-taking process may be considered an inconvenient way for testing, and also the risk of infection is a worrying issue for many people. Therefore, easy operating systems, being noninvasive or minor invasive fluorescent detection technologies, have many interests [50].

Also, in another study, a water-soluble, selective, and sensitive fluorescent probe for glucose detection based on H₂O₂-mediated fluorescence quenching of molybdenum disulfide quantum dots (MoS₂ QDs) was investigated. The MoS₂ QDs were synthesized through an easy hydrothermal method and have water solubility, high stability, bright blue fluorescence, and high quantum yields. Significantly, the fluorescence of MoS₂ QDs is found to be selectively quenched by H₂O₂. Since glucose can be oxidized by glucose oxidase to produce H₂O₂, MoS₂ QDs can be used as a convenient and selective sensor for quantitative detection of glucose. The method was also applied to detect glucose in fetal bovine serum with satisfactory results, suggesting that our approach has great potential application for diabetes mellitus research and clinical diagnosis. In addition, the results provide an alternative platform to design different novel nanosensors to detect other substrates through oxidation by oxygen-dependent oxidase, which could generate H₂O₂ [50].

Glucose oxidase (GOx) catalyzes the glucose oxidation to generate H₂O₂, and the detection of glucose is possible with the fluorescence quenching of MoS₂ QDs by H₂O₂ as the signal transducer. To confirm the PL quenching of MoS₂ QDs by H₂O₂, the PL spectra of MoS₂ QDs in the presence of pure glucose, GOx, and a mixture of glucose and GOx were investigated. It can be found that the fluorescence intensity of MoS₂ QDs appeared no change in the presence of GOx or glucose, but the PL intensity decreased after the addition of glucose-containing 0.2 mg·mL-1 GOx (Figure 7(a)). These results demonstrate that the PL of MoS₂ QDs was quenched by H₂O₂ produced from the GOx-catalyzed oxidation of glucose (Figure 7(b)). Endlessly, the fluorescent focus contracted to raise the whole of glucose usage from 10 to 1500 μM, indicating that the extra H₂O₂ had been acquired with the glucose fixation conveyed (Figure 7(c)). There is a remarkable synchronization association between glucose status and reduced fluorescence (Figure 7(d)).

(a)

(b)

(c)

(d)

Glucose plays a crucial role in living systems; so, blood glucose levels are an essential indicator of human and animal health conditions. To verify the feasibility of our approach to detect glucose in biological samples, it was applied to analyze glucose in fetal bovine serum samples. The glucose solutions with different concentrations of 0.1, 0.8, 1.5, 3.0, and 5.0 mM were added into the MoS₂ QDs/GOx/fetal bovine serum mixture. Then, their fluorescence spectra were investigated. The results showed that the fluorescent intensity decreased gradually with increasing the concentration of glucose (Figure 8). It also can be found from photographs of the MoS2 QDs under 365 nm irradiation (inset of Figure 8) with different concentrations of glucose (0.1, 0.8, 1.5, 3.0, and 5.0 mM). The results revealed that the proposed method is viable for practical blood glucose monitoring in the real sample [48]).

To accept PBS-GQDs as glucose detection agents for diabetes diagnosis, sensing interference from other substances in human serum was studied. And after that, the PBS-GQD glucose sensor was tested on human serum (Figure 9). It was indicated that PBS-GQDs could detect and recognize glucose amongst four other saccharides such as galactose, fructose, sucrose, and lactose [33, 51–55].

5. Glucose Detection in Real Blood Samples

(Figure 5) reveals the quite different fluorescence effects of disaccharides on PBS-GQDs from other monosaccharides. Sucrose and lactose managed to improve the fluorescence effect of PBS-GQDs rather than to reduce it. It is noticeable that the affinity constants (Ka) for binding of the fructose and galactose to the PBS-GQDs are greater than glucose. This suggests that the binding affinity strength is not the definitive parameter in the selective fluorescent detection of glucose. For example, fructose has no additional cis conformational diol unit to further bind with PBS-GQDs to form SQS-contained aggregation though it is easier to combine with PBS-GQDs than glucose [35] covalently. (Table 1) shows the centralizations of glucose gathered, and the accommodating testing office gives the clinical focal points; recoveries reached out from 93.6% to 98%.

6. Fluorescence Resonance Energy Transfer- (FRET-) Based GQD Sensors

As a general rule, weight can be a figure that trades without radiation necessities starting with one fluorophore then onto the next, for example, from a supporter to an acceptor. In an all the more out and out headway, the vitality of the excitation light source is held by the maker. It is not radioactively traded to the acceptor, which is perhaps because of a spike in fluorescence. This subordinate separation feature is used to examine accomplice mixes inside the focal point of bioacknowledgment opportunities [56]. In development to recording, nearby single-cell fixation, worry subordinate sensors were joined to the cell-element board in heterogeneous cell peoples. In any case, in imparting scorn for their specific biomedical uses, these sensors are met with numerous difficulties. There is too an overwhelming requirement for extended affectability close by the advanced fluorescence sureness of Stress biosensors [56, 57].

As delineated in (Figure 10), Qianand partners told an object-based ultra-touchy DNA nanosensor among biogood GQDs and CNTs for target DNA quantitative examination [7, 57, 58]. Right now, progress has been completed by considering: (a) the base-coupling conduct of DNA, (b) specific worry among CNTs and DNA, and (c) vivacious fluorescence and outstanding biocompatibility of GQDs. CNTs and GQDs of QY up to 0.21 have by and by been self-luringly organizes as an equipped extinguishing expert and DNA fluorophore. Cry between oxidized CNTs and GQD evaluation was cultivated by the sensibility of their self-getting together by the stacking of π–ľ. Agreeing to Whine from GQDs and CNTs, regular “on-off” fluorescence was begun from fluorescence extinguishing (30 min) reasonable as the resulting fluorescence recovery (30 min) was because of free twofold stranded (ds) DNA released.

As of late, GQD-sensor subordinate to fluorescence has been showing up to assess the grouped assortment of metal particles, for illustration, Ag⁺, Pb²⁺, Cu², Hg²⁺, and Fe³⁺ particles. These sensors may be sensible for characteristic security to recognize metal particles in water tests to expand clinical affirmation of a few dangerous developments. Sorts for the case, taking after the Fe³⁺ molecule organizes in human serum can offer assistance in danger finding. Interior of the improvement of such sensors, either GQD itself or its functionalized assortments with GO, nitrogen, rhodamine, dopamine, sulfur, boron, amino acids like valine, or for beyond any doubt when gotten at the side nanomaterials, e.g., gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), and sodium citrate-functionalized nanoparticles (Cit-UCNPs), have accomplished interior the bolstered highlights of the person biosensors (Table 2).

The closeness of harming boronic packs on the B-surface can pass on PL for title glucose positioning [12, 58]. Before that, this incites the intramolecular switch, pushing up to a raised PL. Likewise, it has been outlined that B-GQDs can be phenomenally sporadic as glucose instead of isomeric family people, for representation, fructose, mannose, and galactose inferable from their ability to instigate missing from saccharides with as much as one cis-diol band. A short timeframe subsequently tendencies the intramolecular development, inciting an energized PL change. Truly, it has been delineated that B-GQDs can well be essentially remarkable to glucose as confined to its isomeric family people, for the case, fructose, mannose, and galactic [73]. Here, among GQDs and Fe³⁺⁵, 10, 15, 20-tetrakis (1-methyl-4-pyridyl) porphin (FeTMPyP) was wrapped up the production of multifunctional and noncovalent mutts. The GQD’s PL was stifled on the GQDs by FeTMPyP’s inside channel influence (IFE). By then, the stifled PL of GQDs can be traded “up” according to the fitting response that occurred amidst FeTMPyP and H₂O₂ that caused the cyclic tetrapyrrolic focus to break. Fe³⁺ particles from FeTMPyP are lost right directly, dreary mono- and dipyrrole. This “turn-on” estimation framework will give an unquestionable game plan plot to centralizations of glucose and H₂O₂ from 3 to 100 μM and 2 to 300 μM, freely, with an intricacy some spot inside the reach out of 0.5 and 0.3 μM LOD values. Shehab et al. masterminded the usage of phenylboronic harming receptor-GQDs for a nonglucose sensor, where the PL of GQDs was viewed as the key optical parameter for glucose [33]. This sensor may seem a great organized relationship for glucose upkeep fluctuating from 4 to 40 mM (~72 to 720 mg dL−1), with a 3.0 mM LOD. As appeared in (Figure 11), Huang and the bundle proposed another PL-set-up electron move approach depending on the dousing of assorted moving metal particles on GQD focused PL [74].

7. Conclusion

Diabetes could be a metabolic issue, delineated by blood glucose fixations, and causes general take mischief and bafflement of various organs, such as kidney, heart, eyes, and veins. The first and kind affirmation of unusual glucose levels inside the blood is vital for reasonable treatment to diminish different helpful issues. Currently, the accessible glucometers available offer just intrusive, nonconstant measures. Noninvasive, real-time, and advantageous sensors for glucose detection need to be created. An alternate approach may be to merge nanotechnology with fluorescence technologies. Starting late, fluorescent GQDs, one sort of zero-dimensional graphene sheets with sidelong measure under 100 nm, have pulled in examiners since their strong run of the mill and substance dormancy, moo cytotoxicity, and excellent biocompatibility, and insurance. Because of their earth-shattering properties, GQDs are the potential opportunities for bioimaging, invention, and regular recognizing, photocatalysis, and electrocatalysis. The various courses of action frameworks of GQDs were portrayed. In this way, a couple of approaches have been fixated on the social affair, and the glucose biosensors subordinate to glucose oxidase proteins and nitrogen-doped fluorescent GQDs. Biocompatibility and properties of fluorescent nitrogen-doped graphene quantum dots for controlling diabetes have been improved with many years of exertion. For instance, the high quantum yield and photostability of semiconductor quantum dots make them alluring to look into and develop. With the advent of advanced production processes, including three-dimensional (3D) printing and nano/microscale assembly, in noninvasive and/or embedded applications, nanostructured biosensors may be used to provide more efficient data collection models for constant, user-friendly, and real-time glucose control interventions for diabetes. For glucose sensing in the food and pharmaceutical sectors, for the long-term usage of nanostructured glucose biosensors, reliability and longevity in extreme environments such as heat/cold, saline, and acid/primary conditions need to be taken into account.

Data Availability

All data used to support the findings of this study are included within the article.

Conflicts of Interest

The authors declare they have no competing interests.

Acknowledgments

The authors wish to thank Dr. Nasrin Shokrpour at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript. This work was supported by the vice-chancellor of research, Shiraz University of Medical Sciences.

References

F. Emadi, A. Amini, A. Gholami, and Y. Ghasemi, “Functionalized graphene oxide with chitosan for protein nanocarriers to protect against enzymatic cleavage and retain collagenase activity,” Scientific Reports, vol. 7, no. 1, 2017.
View at: Publisher Site | Google Scholar
C. Chen, Q. Xie, D. Yang et al., “Recent advances in electrochemical glucose biosensors: a review,” RSC Advances, vol. 3, no. 14, pp. 4473–4491, 2013.
View at: Publisher Site | Google Scholar
P. Zhang, X. Zhao, Y. Ji et al., “Electrospinning graphene quantum dots into a nanofibrous membrane for dual-purpose fluorescent and electrochemical biosensors,” Journal of Materials Chemistry B, vol. 3, no. 12, pp. 2487–2496, 2015.
View at: Publisher Site | Google Scholar
A. Gholami, M. H. Dabbaghmanesh, Y. Ghasemi, P. Talezadeh, F. Koohpeyma, and N. Montazeri-Najafabady, “Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats,” Diabetology & Metabolic Syndrome, vol. 12, no. 1, 2020.
View at: Publisher Site | Google Scholar
S. M. Mousavi, S. A. Hashemi, M. Zarei et al., “Recent progress in chemical composition, production, and pharmaceutical effects of kombucha beverage: a complementary and alternative medicine,” Evidence-based Complementary and Alternative Medicine, vol. 2020, 14 pages, 2020.
View at: Publisher Site | Google Scholar
S. Jahandideh, M. J. Sarraf Shirazi, M. Tavakoli, S. M. Mousavi, and S. A. Hashemi, “High mechanical and thermal performance of Sasobit-modified epoxy resin, prepared via vacuum shock technique,” Polymer Testing, vol. 81, p. 106171, 2020.
View at: Publisher Site | Google Scholar
S. Mazraedoost and G. Behbudi, “Basic nano magnetic particles and essential oils: biological applications,” Journal of Environmental Treatment Techniques, vol. 9, no. 3, pp. 609–620, 2021.
View at: Google Scholar
R. Masoumzade, G. Behbudi, and S. Mazraedoost, “A medical encyclopedia with new approach graphene quantum dots for anti-breast cancer applications: mini review,” Advances in Applied NanoBio-Technologies, vol. 1, no. 4, pp. 84–90, 2020.
View at: Google Scholar
L. Chen, E. Hwang, and J. Zhang, “Fluorescent nanobiosensors for sensing glucose,” Sensors, vol. 18, no. 5, p. 1440, 2018.
View at: Publisher Site | Google Scholar
S. A. Hashemi, S. M. Mousavi, S. Bahrani, S. Ramakrishna, A. Babapoor, and W. H. Chiang, “Coupled graphene oxide with hybrid metallic nanoparticles as potential electrochemical biosensors for precise detection of ascorbic acid within blood,” Analytica Chimica Acta, vol. 1107, pp. 183–192, 2020.
View at: Publisher Site | Google Scholar
S. Mazraedoost and G. Behbudi, “Nano materials-based devices by photodynamic therapy for treating cancer applications,” Advances in Applied NanoBio-Technologies, vol. 2, no. 3, pp. 9–21, 2021.
View at: Google Scholar
R. Madhu, V. Veeramani, S. M. Chen, A. Manikandan, A. Y. Lo, and Y. L. Chueh, “Honeycomb-like porous carbon–cobalt oxide nanocomposite for high-performance enzymeless glucose sensor and supercapacitor applications,” ACS Applied Materials & Interfaces, vol. 7, no. 29, pp. 15812–15820, 2015.
View at: Publisher Site | Google Scholar
F. Emadi, A. Emadi, and A. Gholami, “A comprehensive insight towards pharmaceutical aspects of graphene nanosheets,” Current Pharmaceutical Biotechnology, vol. 21, no. 11, pp. 1016–1027, 2020.
View at: Publisher Site | Google Scholar
K. Yousefi, N. Parvin, N. Banaei, and S. Mazraedoost, “Water-borne polyurethanes for high-performance electromagnetic interference shielding,” Advances in Applied NanoBio-Technologies, vol. 2, no. 3, pp. 35–45, 2021.
View at: Google Scholar
S. A. Hashemi, N. G. Golab Behbahan, S. Bahrani et al., “Ultra-sensitive viral glycoprotein detection nanosystem toward accurate tracing SARS-CoV-2 in biological/non-biological media,” Biosensors and Bioelectronics, vol. 171, p. 112731, 2021.
View at: Publisher Site | Google Scholar
A. Gholami, S. A. Hashemi, K. Yousefi et al., “3D nanostructures for tissue engineering, cancer therapy, and gene delivery,” Journal of Nanomaterials, vol. 2020, 24 pages, 2020.
View at: Publisher Site | Google Scholar
S. M. Mousavi, S. A. Hashemi, M. Arjmand, A. M. Amani, F. Sharif, and S. Jahandideh, “Octadecyl amine functionalized graphene oxide towards hydrophobic chemical resistant epoxy nanocomposites,” ChemistrySelect, vol. 3, no. 25, pp. 7200–7207, 2018.
View at: Publisher Site | Google Scholar
K. E. Toghill, L. Xiao, M. A. Phillips, and R. G. Compton, “The non-enzymatic determination of glucose using an electrolytically fabricated nickel microparticle modified boron-doped diamond electrode or nickel foil electrode,” Sensors and Actuators B: Chemical, vol. 147, no. 2, pp. 642–652, 2010.
View at: Publisher Site | Google Scholar
S. M. Mousavi, S. A. Hashemi, N. Parvin et al., “Carbon substrates for flexible supercapacitors and energy storage applications,” Flexible Supercapacitor Nanoarchitectonics, pp. 95–141, 2021, https://onlinelibrary.wiley.com/doi/10.1002/9781119711469.ch5.
View at: Publisher Site | Google Scholar
S. A. Hashemi, S. M. Mousavi, R. Faghihi, M. Arjmand, S. Sina, and A. M. Amani, “Lead oxide-decorated graphene oxide/epoxy composite towards X-ray radiation shielding,” Radiation Physics and Chemistry, vol. 146, pp. 77–85, 2018.
View at: Publisher Site | Google Scholar
S. Samuei, J. Fakkar, Z. Rezvani, A. Shomali, and B. Habibi, “Synthesis and characterization of graphene quantum dots/CoNiAl-layered double- hydroxide nanocomposite: application as a glucose sensor,” Analytical Biochemistry, vol. 521, pp. 31–39, 2017.
View at: Publisher Site | Google Scholar
S. Mazraedoost and N. Banaei, “Biochemical composition properties of kombucha SCOBY: mini reviews,” Advances in Applied NanoBio-Technologies, vol. 1, no. 4, pp. 99–104, 2020.
View at: Google Scholar
N. Goudarzian, S. Samiei, F. Safari, S. M. Mousavi, S. A. Hashemi, and S. Mazraedoost, “Enhancing the physical, mechanical, oxygen permeability and photodegradation properties of styrene-acrylonitrile (SAN), butadiene rubber (BR) composite by silica nanoparticles,” Journal of Environmental Treatment Techniques, vol. 8, no. 2, pp. 718–726, 2020.
View at: Google Scholar
J. E. T. Tech, “Investigating the activity of antioxidants activities content in Apiaceae and to study antimicrobial and insecticidal activity of antioxidant by using SPME Fiber assembly carboxen/polydimethylsiloxane (CAR/PDMS),” Journal of Environmental Treatment Techniques, vol. 8, no. 1, pp. 214–224, 2020.
View at: Google Scholar
S. M. Mousavi, S. A. Hashemi, M. Zarei, A. M. Amani, and A. Babapoor, “Nanosensors for chemical and biological and medical applications,” Medicinal Chemistry, vol. 8, no. 8, 2018.
View at: Publisher Site | Google Scholar
S. M. Mousavi, S. A. Hashemi, Y. Ghasemi, A. M. Amani, A. Babapoor, and O. Arjmand, “Applications of graphene oxide in case of nanomedicines and nanocarriers for biomolecules: review study,” Drug Metabolism Reviews, vol. 51, no. 1, pp. 12–41, 2019.
View at: Publisher Site | Google Scholar
A. Zakeri, M. A. J. Kouhbanani, N. Beheshtkhoo et al., “Polyethylenimine-based nanocarriers in co-delivery of drug and gene: a developing horizon,” Nano Reviews & Experiments, vol. 9, no. 1, p. 1488497, 2018.
View at: Publisher Site | Google Scholar
Y. Dong, J. Shao, C. Chen et al., “Blue luminescent graphene quantum dots and graphene oxide prepared by tuning the carbonization degree of citric acid,” Carbon, vol. 50, no. 12, pp. 4738–4743, 2012.
View at: Publisher Site | Google Scholar
R. Liu, D. Wu, X. Feng, and K. Müllen, “Bottom-up fabrication of photoluminescent graphene quantum dots with uniform morphology,” Journal of the American Chemical Society, vol. 133, no. 39, pp. 15221–15223, 2011.
View at: Publisher Site | Google Scholar
P. N. Joshi, S. Kundu, S. K. Sanghi, and D. Sarkar, “Graphene quantum dots-from emergence to nanotheranostic applications, in smart drug delivery system,” in Smart Drug Delivery System, pp. 159–195, INTECH, 2016.
View at: Publisher Site | Google Scholar
X. Wu, F. Tian, W. Wang, J. Chen, M. Wu, and J. X. Zhao, “Fabrication of highly fluorescent graphene quantum dots using L-glutamic acid for in vitro/in vivo imaging and sensing,” Journal of Materials Chemistry C, vol. 1, no. 31, pp. 4676–4684, 2013.
View at: Publisher Site | Google Scholar
L. Wang and H. S. Zhou, “Green synthesis of luminescent nitrogen-doped carbon dots from milk and its imaging application,” Analytical Chemistry, vol. 86, no. 18, pp. 8902–8905, 2014.
View at: Publisher Site | Google Scholar
M. Shehab, S. Ebrahim, and M. Soliman, “Graphene quantum dots prepared from glucose as optical sensor for glucose,” Journal of Luminescence, vol. 184, pp. 110–116, 2017.
View at: Publisher Site | Google Scholar
L. Ponomarenko, F. Schedin, M. I. Katsnelson et al., “Chaotic dirac billiard in graphene quantum dots,” Science, vol. 320, no. 5874, pp. 356–358, 2008.
View at: Publisher Site | Google Scholar
J. Peng, W. Gao, B. K. Gupta et al., “Graphene quantum dots derived from carbon fibers,” Nano Letters, vol. 12, no. 2, pp. 844–849, 2012.
View at: Publisher Site | Google Scholar
A. Gholami, F. Emadi, A. Amini, M. Shokripour, M. Chashmpoosh, and N. Omidifar, “Functionalization of graphene oxide nanosheets can reduce their cytotoxicity to dental pulp stem cells,” Journal of Nanomaterials, vol. 2020, 14 pages, 2020.
View at: Publisher Site | Google Scholar
Y. Li, Y. Hu, Y. Zhao et al., “An electrochemical avenue to green-luminescent graphene quantum dots as potential electron-acceptors for photovoltaics,” Advanced Materials, vol. 23, no. 6, pp. 776–780, 2011.
View at: Publisher Site | Google Scholar
L. Bao, Z. L. Zhang, Z. Q. Tian et al., “Electrochemical tuning of luminescent carbon nanodots: from preparation to luminescence mechanism,” Advanced Materials, vol. 23, no. 48, pp. 5801–5806, 2011.
View at: Publisher Site | Google Scholar
S. Zhu, Y. Song, J. Wang et al., “Photoluminescence mechanism in graphene quantum dots: quantum confinement effect and surface/edge state,” Nano Today, vol. 13, pp. 10–14, 2017.
View at: Publisher Site | Google Scholar
M. Mitchell, “New nanoparticles bring cheaper, lighter solar cells outdoors,” pp. 8–24, 2014, Rdmag.com.
View at: Google Scholar
Y. Xuan, R. Y. Zhang, X. S. Zhang et al., “Targeting N-doped graphene quantum dot with high photothermal conversion efficiency for dual-mode imaging and therapy in vitro,” Nanotechnology, vol. 29, no. 35, p. 355101, 2018.
View at: Publisher Site | Google Scholar
Y. Du and S. Guo, “Chemically doped fluorescent carbon and graphene quantum dots for bioimaging, sensor, catalytic and photoelectronic applications,” Nanoscale, vol. 8, no. 5, pp. 2532–2543, 2016.
View at: Publisher Site | Google Scholar
C.-B. Ma, Z. T. Zhu, H. X. Wang et al., “A general solid-state synthesis of chemically-doped fluorescent graphene quantum dots for bioimaging and optoelectronic applications,” Nanoscale, vol. 7, no. 22, pp. 10162–10169, 2015.
View at: Publisher Site | Google Scholar
Y. F. Kang, Y. H. Li, Y. W. Fang, Y. Xu, X. M. Wei, and X. B. Yin, “Carbon quantum dots for zebrafish fluorescence imaging,” Scientific Reports, vol. 5, no. 1, pp. 1–12, 2015.
View at: Google Scholar
X. Gong, W. Lu, M. C. Paau et al., “Facile synthesis of nitrogen-doped carbon dots for Fe³⁺ sensing and cellular imaging,” Analytica Chimica Acta, vol. 861, pp. 74–84, 2015.
View at: Publisher Site | Google Scholar
A. Ananthanarayanan, Y. Wang, P. Routh et al., “Nitrogen and phosphorus co-doped graphene quantum dots: synthesis from adenosine triphosphate, optical properties, and cellular imaging,” Nanoscale, vol. 7, no. 17, pp. 8159–8165, 2015.
View at: Publisher Site | Google Scholar
L. Lin, X. Song, Y. Chen et al., “Intrinsic peroxidase-like catalytic activity of nitrogen-doped graphene quantum dots and their application in the colorimetric detection of H₂O₂ and glucose,” Analytica Chimica Acta, vol. 869, pp. 89–95, 2015.
View at: Publisher Site | Google Scholar
W. Guan, W. Zhou, J. Lu, and C. Lu, “Luminescent films for chemo- and biosensing,” Chemical Society Reviews, vol. 44, no. 19, pp. 6981–7009, 2015.
View at: Publisher Site | Google Scholar
P. D. Howes, R. Chandrawati, and M. M. Stevens, “Colloidal nanoparticles as advanced biological sensors,” Science, vol. 346, no. 6205, 2014.
View at: Publisher Site | Google Scholar
X. Wang, Q. Wu, K. Jiang, C. Wang, and C. Zhang, “One-step synthesis of water-soluble and highly fluorescent MoS₂ quantum dots for detection of hydrogen peroxide and glucose,” Sensors and Actuators B: Chemical, vol. 252, pp. 183–190, 2017.
View at: Publisher Site | Google Scholar
X. Ran, H. Sun, F. Pu, J. Ren, and X. Qu, “Ag nanoparticle-decorated graphene quantum dots for label-free, rapid and sensitive detection of Ag+ and biothiols,” Chemical Communications, vol. 49, no. 11, pp. 1079–1081, 2013.
View at: Publisher Site | Google Scholar
S. Zhu, J. Zhang, S. Tang et al., “Surface chemistry routes to modulate the photoluminescence of graphene quantum dots: from fluorescence mechanism to up-conversion bioimaging applications,” Advanced Functional Materials, vol. 22, no. 22, pp. 4732–4740, 2012.
View at: Publisher Site | Google Scholar
M. Mirzababaei, K. Larijani, H. Hashemi-Moghaddam, Z. Mirjafary, and H. Madanchi, “In vitro targeting of NL2 peptide bounded on poly L-DOPA coated graphene quantum dot,” Journal of Fluorescence, vol. 31, no. 1, pp. 279–288, 2021.
View at: Publisher Site | Google Scholar
G. Lui, J. Y. Liao, A. Duan, Z. Zhang, M. Fowler, and A. Yu, “Graphene-wrapped hierarchical TiO 2 nanoflower composites with enhanced photocatalytic performance,” Journal of Materials Chemistry A, vol. 1, no. 39, pp. 12255–12262, 2013.
View at: Publisher Site | Google Scholar
W. Wu, T. Zhou, A. Berliner, P. Banerjee, and S. Zhou, “Glucose-mediated assembly of phenylboronic acid modified CdTe/ZnTe/ZnS quantum dots for intracellular glucose probing,” Angewandte Chemie International Edition, vol. 49, no. 37, pp. 6554–6558, 2010.
View at: Publisher Site | Google Scholar
S. Zadran, S. Standley, K. Wong, E. Otiniano, A. Amighi, and M. Baudry, “Fluorescence resonance energy transfer (FRET)-based biosensors: visualizing cellular dynamics and bioenergetics,” Applied Microbiology and Biotechnology, vol. 96, no. 4, pp. 895–902, 2012.
View at: Publisher Site | Google Scholar
Z. S. Qian, X. Y. Shan, L. J. Chai, J. J. Ma, J. R. Chen, and H. Feng, “DNA nanosensor based on biocompatible graphene quantum dots and carbon nanotubes,” Biosensors and Bioelectronics, vol. 60, pp. 64–70, 2014.
View at: Publisher Site | Google Scholar
Z. S. Qian, X. Y. Shan, L. J. Chai, J. J. Ma, J. R. Chen, and H. Feng, “A universal fluorescence sensing strategy based on biocompatible graphene quantum dots and graphene oxide for the detection of DNA,” Nanoscale, vol. 6, no. 11, pp. 5671–5674, 2014.
View at: Publisher Site | Google Scholar
F. Wang, Z. Gu, W. Lei, W. Wang, X. Xia, and Q. Hao, “Graphene quantum dots as a fluorescent sensing platform for highly efficient detection of copper(II) ions,” Sensors and Actuators B: Chemical, vol. 190, pp. 516–522, 2014.
View at: Publisher Site | Google Scholar
Z. S. Qian, X. Y. Shan, L. J. Chai, J. R. Chen, and H. Feng, “A fluorescent nanosensor based on graphene quantum dots-aptamer probe and graphene oxide platform for detection of lead (II) ion,” Biosensors and Bioelectronics, vol. 68, pp. 225–231, 2015.
View at: Publisher Site | Google Scholar
X. Niu, Y. Zhong, R. Chen, F. Wang, Y. Liu, and D. Luo, “A "turn-on" fluorescence sensor for Pb²⁺ detection based on graphene quantum dots and gold nanoparticles,” Sensors and Actuators B: Chemical, vol. 255, pp. 1577–1581, 2018.
View at: Publisher Site | Google Scholar
N. T. N. Anh, A. D. Chowdhury, and R.-a. Doong, “Highly sensitive and selective detection of mercury ions using N, S-codoped graphene quantum dots and its paper strip based sensing application in wastewater,” Sensors and Actuators B: Chemical, vol. 252, pp. 1169–1178, 2017.
View at: Publisher Site | Google Scholar
Z. Xiaoyan, L. Zhangyi, and L. Zaijun, “Fabrication of valine-functionalized graphene quantum dots and its use as a novel optical probe for sensitive and selective detection of Hg^{2 +},” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 171, pp. 415–424, 2017.
View at: Publisher Site | Google Scholar
S. Bian, C. Shen, Y. Qian, J. Liu, F. Xi, and X. Dong, “Facile synthesis of sulfur-doped graphene quantum dots as fluorescent sensing probes for Ag⁺ ions detection,” Sensors and Actuators B: Chemical, vol. 242, pp. 231–237, 2017.
View at: Publisher Site | Google Scholar
X.-E. Zhao, C. Lei, Y. Gao et al., “A ratiometric fluorescent nanosensor for the detection of silver ions using graphene quantum dots,” Sensors and Actuators B: Chemical, vol. 253, pp. 239–246, 2017.
View at: Publisher Site | Google Scholar
L. He, L. Yang, H. Zhu, W. Dong, Y. Ding, and J. J. Zhu, “A highly sensitive biosensing platform based on upconversion nanoparticles and graphene quantum dots for the detection of Ag+,” Methods and applications in fluorescence, vol. 5, no. 2, article 024010, 2017.
View at: Publisher Site | Google Scholar
J. Ju and W. Chen, “Synthesis of highly fluorescent nitrogen-doped graphene quantum dots for sensitive, label-free detection of Fe (III) in aqueous media,” Biosensors and Bioelectronics, vol. 58, pp. 219–225, 2014.
View at: Publisher Site | Google Scholar
R. Guo, S. Zhou, Y. Li, X. Li, L. Fan, and N. H. Voelcker, “Rhodamine-functionalized graphene quantum dots for detection of Fe3+ in cancer stem cells,” ACS Applied Materials & Interfaces, vol. 7, no. 43, pp. 23958–23966, 2015.
View at: Publisher Site | Google Scholar
T. Van Tam, N. B. Trung, H. R. Kim, J. S. Chung, and W. M. Choi, “One-pot synthesis of N-doped graphene quantum dots as a fluorescent sensing platform for Fe³⁺ ions detection,” Sensors and Actuators B: Chemical, vol. 202, pp. 568–573, 2014.
View at: Publisher Site | Google Scholar
S. Ge, J. He, C. Ma, J. Liu, F. Xi, and X. Dong, “One-step synthesis of boron-doped graphene quantum dots for fluorescent sensors and biosensor,” Talanta, vol. 199, pp. 581–589, 2019.
View at: Publisher Site | Google Scholar
A. Dutta Chowdhury and R. A. Doong, “highly sensitive and selective detection of nanomolar ferric ions using dopamine functionalized graphene quantum dots,” ACS Applied Materials & Interfaces, vol. 8, no. 32, pp. 21002–21010, 2016.
View at: Publisher Site | Google Scholar
S. Li, Y. Li, J. Cao, J. Zhu, L. Fan, and X. Li, “Sulfur-doped graphene quantum dots as a novel fluorescent probe for highly selective and sensitive detection of Fe3+,” Analytical Chemistry, vol. 86, no. 20, pp. 10201–10207, 2014.
View at: Publisher Site | Google Scholar
L. Zhang, D. Peng, R. P. Liang, and J. D. Qiu, “Graphene quantum dots assembled with metalloporphyrins for “Turn on” sensing of hydrogen peroxide and glucose,” Chemistry–A European Journal, vol. 21, no. 26, pp. 9343–9348, 2015.
View at: Publisher Site | Google Scholar
Y. Li, Y. Jiang, T. Mo, H. Zhou, Y. Li, and S. Li, “Highly selective dopamine sensor based on graphene quantum dots self-assembled monolayers modified electrode,” Journal of Electroanalytical Chemistry, vol. 767, pp. 84–90, 2016.
View at: Publisher Site | Google Scholar
H. Huang, L. Liao, X. Xu, M. Zou, F. Liu, and N. Li, “The electron-transfer based interaction between transition metal ions and photoluminescent graphene quantum dots (GQDs): a platform for metal ion sensing,” Talanta, vol. 117, pp. 152–157, 2013.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Seyyed Mojtaba Mousavi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

3210

Downloads

1371

Citations