Open access peer-reviewed chapter

Quantum Dots in Cancer Cell Imaging

Written By

Salar Khaledian, Mohadese Abdoli, Reza Fatahian and Saleh Salehi Zahabi

Submitted: 02 August 2022 Reviewed: 02 September 2022 Published: 20 January 2023

DOI: 10.5772/intechopen.107671

From the Edited Volume

Quantum Dots - Recent Advances, New Perspectives and Contemporary Applications

Edited by Jagannathan Thirumalai

Chapter metrics overview

249 Chapter Downloads

View Full Metrics

Abstract

Research on quantum dots (QDs) as zero-dimensional nanostructures whose size is not more than a few nanometers has accelerated in the last two decades, especially in the field of medicine. These nanostructures have attracted much attention due to their unique features such as broad excitation range, narrow emission, strong fluorescence, and high resistance to photobleaching. In this chapter, besides common QDs such as cadmium (Cd)-containing semiconductor QDs, other QDs including carbon-based QDs, chalcogenide QDs, and black phosphorus QDs will be discussed. In addition to describing the optical characteristics of these nanostructures, the usual synthesis methods, their modification and cytotoxicity will be reviewed. Finally, the application of each category of QDs in cancer cell imaging will prospect in more detail.

Keywords

  • cell imaging
  • semiconductor QDs
  • carbon-based QDs
  • MoS2 QDs
  • black phosphorus QDs

1. Introduction

Cancer is one of the main causes of death all over the world, and after cardiovascular diseases, it is the most common cause of death. This disease is usually caused by defects in the functioning of the regulatory mechanisms of the process of cell growth and division [1]. In the United States alone, 600,000 people die from cancer each year and 1.7 million new cases are diagnosed [2]. Reducing mortality, increasing survival, improving patients, quick diagnosis, and then timely and specific treatments are the keys to success in cancer treatment [3]. Early diagnosis of cancer is important because the length of the treatment period is shortened and treatment costs are reduced. In addition, some cancers are aggressive and asymptomatic in their early stages, and their rapid detection can be very critical [4]. Microscopic imaging techniques (optical and fluorescence), despite having advantages such as inexpensiveness, non-invasive, and ease of use, also have limitations, among which the emission of fluorescence from cancer cell proteins and also the short time of fluorescence emission. The use of small fluorescent dyes (such as 5-aminolevulinic acid, methylene blue, and indocyanine green) can be an entrepreneur in this regard, but cytotoxicity, photobleaching, and rapid clearance through the lymph system limit their use [5]. Clinical methods of cancer imaging include X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), etc., which, despite providing appropriate morphological data of cancer cells and tissue, but in cases where the cancer tissue is very similar to healthy tissue, the resolution and contrast are not appropriate [6, 7]. Therefore, the development of probes that overcome the challenges associated with signal intensity, stability, and tissue penetration will be essential for more extensive clinical implementation. QDs, often described as “artificial atoms,” are semiconductor nanocrystals that are in the nanoscale region in all dimensions (so-called zero-dimensional nanostructures) and have a size less than 10 nm [8]. Tunable emission into the NIR region, broad excitation range, narrow emission, and a large Stokes shift, high photoluminescence quantum yield, long photoluminescence lifetime and compatible with biomolecular functionalization and the EPR effect among the attractive optical characteristics of QDs as fluorescent imaging probes [2]. Participation in reactions as catalysts or energy acceptor, or direct oxidation and simultaneous energy transfer are among the mechanisms of QDs to enhance signal intensity [9]. Furthermore, light emission for broad-spectrum excitation of the QDs, emits light at a longer wavelength and enhances tissue penetration [10]. In addition, due to the large surface area of QDs, they can covalently link to biorecognition molecules, such as peptides, antibodies, nucleic acids, or small-molecule ligands for further application as fluorescent probes [11, 12]. Molecular beam epitaxy (MBE), ion implantation, electron-beam lithography, X-ray lithography, wet-chemical, and vapor-phase methods are common methods of quantum dot synthesis, which fall into two general categories: top-down and bottom-up [5]. In the last years, QDs have been extensively studied in biosensing, in vitro diagnosis, cancer treatment, bioimaging, drug delivery, etc. [13, 14, 15, 16]. Currently, QDs are widely used for optical imaging of cancer cells, which has great significance for clinical diagnosis. Herein, we briefly introduce typical QDs (semiconductor QDs, carbon-based QDs, chalcogenide QDs and black phosphorus QDs), review the different synthesis methods and modifications, and analyze their cytotoxicity. Finally, the applications of QDs in cancer cell imaging are prospected.

Advertisement

2. Semiconductor QDs (SQDs): synthesis methods, modification, cytotoxicity, and application in cancer cell imaging

This class of QDs is usually core-shell (Figure 1), in the primary classification, the biocompatible fluorescent core consists of elements from groups II–IV, for example, CdSe, or groups III–V, for example, InP and is covered by a semiconductor shell which improves efficiency and photostability (ZnS, ZnSe). Finally, a variable outer layer such as silica can offer a large surface area for surface functionalization that enables their dispersion in water, and functionalized with other biomolecules (like peptides, antibodies, nucleic acids, and small-molecule ligands) to target specific proteins expressed on the surface of the cancer cells [12, 18, 19].

Figure 1.

Schematic diagram of SQDs structure; QDs consist of an inorganic (fluorescent) core, an inorganic shell, and aqueous organic coating [17].

The methods of synthesizing SQDs are different depending on the used material, desired size, quantum yield and their applications [20]. Synthesis through high temperature, synthesis through γ-Irradiation, microwave-assisted method, sol–gel technique, and core-shell technique are among the common methods for synthesis of SQDs. In the high-temperature method, the NaHTe solution (mixture of potassium tellurite and sodium borohydride which were previously heated under N2 protection) was injected into the N2-saturated Cd2+–MSA–alginate precursor. Then, the reaction mixture was heated to reflux (100°C) under atmospheric conditions with a condenser attached for different time intervals. Finally, the as-prepared CdTe alginate QDs were precipitated with ethanol, collected via centrifugation and dispersed in distilled water [21]. In the gamma irradiation method, the aqueous solution containing CdCl2 and SeO2 is aerated under N2. Then the solution is irradiated with gamma ray. After irradiation, the synthesized quantum dots are separated by centrifugation at 10,000 for 5 min [22]. In the microwave-assisted method, the 3-mercaptopropionic acid is added to an N2-saturated CdCl2 solution (solution 1). Then the desired pH is adjusted using NaOH (about 11). After that, the freshly prepared NaHTe solution is added to solution 1 and exposed to microwave irradiation at 120°C for 2–5 min to obtain monodispersed CdTe core QDs. Next, the GSH is added to an N2-saturated CdCl2 solution (solution 2) and adjusted pH to 11 by NaOH. Then freshly prepared NaHSe solution is added to solution 2 and exposed to microwave irradiation at 60°C for 3–20 min to obtain CdTe/CdSe core/shell QDs [23]. In the sol–gel technique, the materials exist in solution form and grow at low temperature to form a wet gel. This technique is utilized for the formation of Au, Cu, and Zn QDs [20]. In the core-shell technique, synthesis is done by the formation of metal droplet precursor and intermediate growth on the surface of quantum dots [20].

In order to increase the luminous efficiency and stability of QDs, some modifications are made on their surface. Organic modification of SQDs which include organic ligand, organic polymer, proteins, and other organics modifiers. Inorganic modifications that include elements such as Co2+, Ni2+, Mn2+, and Cu2+ doped into SQDs [24]. SQDs, especially Cadmium (Cd)-containing QDs, despite having effects such as high sensitivity and strong stability, but due to cytotoxicity, especially in normal cells, they are not very effective in cell imaging [25]. The released Cd ions are highly toxic and lead to cell damage. In addition, the small size of nanoparticles is also very important, where studies have shown that CdTe-QDs with a size of 2.2 nm are more toxic than large particles with a size of 5.2 nm [26]. Furthermore, different studies indicated that CdTe QDs cause damage to the DNA of HUVEC cells by inducing the production of reactive oxygen species (ROS) [27]. Thus, this type of QDs due to having heavy metals cannot be used for clinical treatment. Therefore, Copper indium sulfide (CuInS2, CIS) QDs proposed as a non-toxic and potential alternative. CIS QDS with a ZnS shell (CIS/ZnS) have a high photoluminescence quantum yield that can be easily transferred in aqueous medium and facilitate their application in biological imaging [25]. Liu et al. synthesized CuInS2/ZnS QDs as a near-infrared (NIR) fluorescence nanoprobe. They used Arg-Gly-Asp (RGD)-labeled bovine serum albumin-poly (ε-caprolactone)-coated CuInS2/ZnS QDs to further evaluate the cytotoxicity and in vitro tumor targeting in U87 and HeLa cells. As shown in Figure 2A, the presence of cRGD significantly increases the internalization of QDs in two kinds of cancer cells. In addition, BSA as an outer shell QDs, significantly reduced non-specific cellular binding and improved biocompatibility [28]. In another study, Kim et al. synthesized Cd-free high-quality CuInS2/ZnS core/shell QDs and used for in vivo tumor targeting in RR1022 cancer cell xenograft mice (Figure 2B). Their results showed that after intravenous injection of cRGDyk-GCM-QDs, the NIR fluorescence emission increased with time in the supine and prone positions of the mice which indicates high tumor uptake [29]. In the study conducted by Zhao et al., the ability to use GSH-capped CuInS2/ZnS QDs in cancer cell imaging was investigated (Figure 2C). Their results indicated that the CuInS2/ZnS QDs can enter the cell and most of them were in the cytoplasm [30]. Previous studies have shown that CIS QDs without ZnS shells rapidly degrade and cause significant toxicity in blood chemistry, organ weight, and histology. Therefore, more caution should be taken in clinical practice [31].

Figure 2.

Application of CuInS2 QDs in cancer cell imaging. (A) Confocal fluorescence image of U87 and HeLa cells treated with nontargeting nanoprobe (a, c), and treated with cRGD-functionalized nanoprobe (b, d). reprinted with permission from [26]. (B) NIR fluorescence images of RR1022 tumor-bearing mouse after intravenous injection with cRGDyk-GCM-QDs. reprinted with permission from [27]. (C) Confocal fluorescence image of MCF10CA1a breast tumor cells treated with GSH-capped CuInS2/ZnS QDs. reprinted with permission from [28].

Advertisement

3. Carbon-based QDs: synthesis methods, modification, cytotoxicity, and application in cancer cell imaging

Carbon-based quantum dots include a wide group, which is discussed more in this chapter on carbon quantum dots (CQDs) and graphene quantum dots (GQDs) (Figure 3). CQDs, also called carbon dots, are a new category of carbon nanomaterials with a size below 10 nm that were first discovered in 2004 [32]. The shape of CQDs, is spherical and has a crystal lattice with surface chemical groups, which possess quantum confinement effect (QCE) and intrinsic state luminescence [33]. A major feature of quantum dots is the QCE, which occurs when quantum dots are smaller than their exciton Bohr radius. According to the results of previous studies, it seems that the small size (below 10 nm) and the increase in the thickness of the shell in quantum dots create a strong confinement effect, which ultimately increases the amount of luminescence [34, 35, 36]. In addition to having excellent optical properties, CQDs are less cytotoxic, environmental, and biohazardous than traditional semiconductor quantum dots. Moreover, in addition, CQDs have good water solubility, chemical stability, and photobleaching resistance, ease of surface functionalization, and large-scale preparation [37]. This group of quantum dots is widely used in the field of biosensing and bioimaging [38, 39]. GQDs is one of the most attractive and newest members of the graphene family, which have an exposed graphene network and are composed of single or multiple sheets of graphene fragments [40]. This type of QDs has many applications in the field of biomedical, including cell imaging [41].

Figure 3.

Schematic diagram of the structure of carbon-based QDs.

The synthesis methods of both quantum dots are almost similar and include: acidic exfoliation method, laser ablation, hydrothermal method, solvothermal method, electrochemical method, precursor pyrolysis, microwave-assisted synthesis chemical vapor deposition (CVD), etc. [5, 42]. The most common and important synthesis methods are shown in Figures 4 and 5. In CQDs, due to having oxygen-containing groups, the possibility of covalent bonding with other functional groups is very high. Covalent bonding by chemical agents such as amine groups is a current approach for surface modification of CQDs [43]. In the case of GQDs, surface functionalization with folic acid, arginine-glycine-aspartic acid (RGD) and polyethyleneimine (PEI) were performed in recent years [5].

Figure 4.

The typical approaches for the synthesis of CQDs. (A) hydrothermal method, (B) chemical oxidation, (C) emulsion-templated carbonization, (D) chemical vapor deposition, (E) hydrothermal method, (F) microwave-assisted pyrolysis synthesis method. Reprinted with permission from [36].

Figure 5.

The typical approaches for the synthesis of GQDs [5].

Previous studies in the in vitro and in vivo showed that both QDs at low concentrations have little cytotoxicity even if are synthesized from toxic ingredients [44]. The size and concentration of quantum dots are two important factors that affect cytotoxicity [45]. For example, it has been reported that GQDs with a concentration of less than 50 μg/ml have less than 10% cytotoxicity, while at a concentration of 200 μg/ml, they have more than 20% cytotoxicity [46].

Carbon-based quantum dots are used in various fields such as environment, energy, sensing, and imaging. Wang et al. synthesized polymer-coated nitrogen-doped carbon nanodots by direct solvothermal reaction. The CQDs were stable and water soluble with a particle size in the range of 5–15 nm. The prepared quantum dots did not show obvious cytotoxicity. In the in vivo study that was performed on the glioma-bearing nude mice, the high fluorescence emission was observed at 30-min post injection of the pN-CNDs (Figure 6A). They stated that surface coating of the QDs with a hydrophilic polymer, in addition to increasing the accumulation of the particles in the glioma, extended the circulation time in the bloodstream, which increases the chance of binding to the target tumor site [47]. In another study Li and co-worker showed that CQDs functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumors), selectively accumulate in human tumor xenografts in mice and in an orthotopic mouse model of human glioma. They reported that 8 h after intravenous injection into mice bearing HeLa tumors, maximum fluorescence emission was observed in the tumor area, while no fluorescence was observed in other areas (Figure 6B). In order to investigate the capability of LAAM TC-CQDs for brain cancer imaging and treatment, the prepared CQDs injected intravenously into mice bearing U87 gliomas. Their results showed the maximum accumulation of carbon quantum dots in the brain occurs 8–12 h after injection. In addition, by euthanizing the mice after 12 h, ex vivo results showed that LAAM TC-CQDs were significantly accumulated in the brain tumor compared to other organs (Figure 6C) [48]. In one study, the GQD–europium complex composites was used as a probe for in vivo fluorescence imaging of HeLa tumor-bearing nude mice. They stated that the maximum amount of fluorescence emission occurs at the tumor site 2 h after injection. While fluorescence is not observed in other organs (Figure 7A) [49]. Wang et al. reported that Folic acid (FA)-conjugated GQDs were capable to selective imaging of Hela cancer cell in comparison to A549 and HEK293A cell line (Figure 7B). Their result showed that GQD–FA enter to Hela cells with FR-induced endocytosis, which is consistent with the fact that HeLa cells overexpress FR while A549 and HEK293A express FR at a low level [50].

Figure 6.

Application of CQDs in cancer cell imaging. (A) In- and ex-vivo imaging of glioma-bearing mice intravenously administered with the pN-CNDs. reprinted with permission from [41]. (B) NIR fluorescence images of a representative mouse bearing a HeLa tumor that received intravenous injection of LAAM TC-CQDs at the indicated time points. (C) In- and ex-vivo NIR fluorescence images of a representative U87-tumor-bearing mouse (a) and indicated organs and tumor (b) after intravenous injection of LAAM TC-CQDs at the indicated time points. Reprinted with permission from [42].

Figure 7.

Application of GQDs in cancer cell imaging. (A) In vivo imaging of HeLa tumor-bearing nude mice after injection of (GQD/DBM)3EuPhen/GQD (5 mg/kg) (a). Ex vivo images of isolated organs of mice at 10 h after injection (b) and PL intensities of (GQD/DBM)3EuPhen/GQD from isolated organs (c). Reprinted with permission from [43]. (B) Confocal laser scanning microscopy of Hela, A549, and HEK293A cells incubated with GQD–FA. Reprinted with permission from [44].

Advertisement

4. Chalcogenide QDs: synthesis methods, modification, cytotoxicity, and application in cancer cell imaging

Beside to graphene and graphene oxide [51], transition metal dichalcogens (TMDs), which belong to a large family of layered compounds, have attracted a lot of attention in the field of drug delivery and imaging [52, 53]. Among TMDs, molybdenum disulfide (MoS2) is used more than in the fields of drug delivery, sensing and imaging [54, 55]. MoS2 QDs due to features such as water-solubility, biocompatibility, high stability, less toxicity, and high surface-area has attracted enormous interest [5657]. There are many methods for the preparation of MoS2 QDs, including chemical intercalation, electrochemical exfoliation, liquid solvent exfoliation, electron Fenton reaction, and hydrothermal reaction which are shown in Figure 8.

Figure 8.

The typical approaches for the synthesis of MoS2 QDs.

Several studies have investigated the use of MoS2 QDs in cancer cell imaging. Roy et al. used free folic acid-sensitive MoS2 QDs based “turn-off” nanoprobes for bioimaging of cancer cells. Their results showed that the FA-pretreated B16F10 cancer cells show higher population of dimmed fluorescence compared to untreated cancer cells and HEK-293 normal cells (Figure 9A) [58]. In another study, Liu and colleagues produced MoS2 QDs through a facile one-step and low cost and green method for bioimaging applications. They reported that blue luminescence was observed inside the HeLa cells, indicating that the QDs had penetrated the cell and mainly localized in the cytoplasm region (Figure 9B). In addition, they stated that molybdenum disulfide quantum dots were not toxic on cells and the morphology of cells remained normal [59]. Shi and co-worker introduced a Bottom-up hydrothermal approach for the preparation of MoS2 QDs with Na2MoO4 2H2O as molybdenum source and GSH as sulfur source. The in vitro result showed that blue fluorescence was observed in the cytoplasm of SW480 cells, which indicating that GSH-MoS2 QDs has successfully entered the cell. In the in vivo study, the GSH-MoS2 QDs were injected into the mice with colon cancer via the tail vein. After the injection of QDs, the contrast of the tumor area increased and the environment around the tumor became blue (Figure 9C). In addition, the results of the biocompatibility test as well as histological analysis showed that GSH-MoS2 QDs do not have obvious toxicity on SW480 cells and no abnormality was observed in different tissues such as heart, kidney, and lung [60].

Figure 9.

Application of MoS2 QDs in cancer cell imaging. (A) Confocal microscopic images of HEK-293 and B16F10 cells after treating MoS2 QDs in FA-pretreated and untreated cells. Reprinted with permission from [51]. (B) Confocal fluorescence microphotograph of HeLa cells incubated with MoS2 QDs. Reprinted with permission from [52]. (C) In vitro fluorescence imaging of SW480 tumor cells with MoS2QDs; in vivo fluorescence images of mice bearing renal carcinoma tumors pre- and post-injection (1 h and 24 h) of MoS2QDs. The red circle in pictures indicated tumor region. Reprinted with permission from [53].

Advertisement

5. Black phosphorus QDs: synthesis methods, modification, cytotoxicity, and application in cancer cell imaging

Black phosphorus (BP) is another two-dimensional nanostructure that has attracted a lot of attention in less than a decade [52, 61]. like graphene, BP is composed of only one element (phosphorus) and is widely used in bioimaging and drug delivery due to its high biocompatibility, biological activity, biodegradability [6263]. Due to the high surface-to-volume ratio, BP nanosheets are highly efficient in loading anticancer drugs. In addition, with excellent photothermal conversion efficiency, BP nanosheets generate heat locally under laser irradiation in the NIR region, which can be used in photothermal therapy (PTT) of cancer [64, 65]. Also, due to its unique electronic structure, BP can be used as a photosensitizer to produce singlet oxygen and be effective in photodynamic therapy (PDT) of cancer [66, 67]. Moreover, BP nanosheets can also be used for photoacoustic imaging of tumors [68]. Black Phosphorus Quantum Dots (BPQDs) are a metal-free layered semiconductor derived from BP nanosheets that were first introduced in 2015 [69, 70]. There are many ways for synthesis of BPQDs, including ultrasonic exfoliation, electrochemical exfoliation, solvothermal, milling crash, blender breaking and pulsed laser irradiation, which classified into two general categories: top-down and bottom-up methods (Figure 10). Since BPQDs are not very stable in aqueous environment and may react with oxygen and oxidize, their surface modification should be done. Polymer modified black phosphorus quantum dot, assembly off quantum dot in device, quantum dot molecule complex, quantum dot doping film and quantum dot nanosheet hybrid are among the common modifications that can be performed on black phosphorus quantum dot [5].

Figure 10.

The typical approaches for the synthesis of BPQDs [5].

Several studies have shown that BPQDs have negligible cytotoxicity. However Gui et al. reported that BPQDs at a concentration up to 200 mg/mL had significant apoptotic effects on HeLa cells [69]. This type of QDs has many applications in fluorescence, photoacoustic, and thermal imaging of cancer cells [5]. In one study Li et al. reported that in the presence of RdB/PEG-BPQDs, the distinct fluorescence signals were observed in Hep G2 cells and 4 T1 cells (Figure 11A). Their observations also showed that the QDs were located almost exclusively in the cytoplasm, and no visible fluorescence was observed in cancer cells without the nanoprobes [71]. Wang and colleagues synthesized BPQDs modified with poly ethylene glycol and folic acid for cancer imaging. There in vitro experiment showed that the fluorescence was initially observed in the cytoplasm and was observed in the nucleus (Figure 11B). In addition, the thermal image indicated that after 4 h intravenous injection of FA-PEG@BPQD@DOX, the temperature of tumor site was reached to 56.8°C, which is sufficient for killing tumor cells (Figure 11C) [72].

Figure 11.

Application of BPQDs in cancer cell imaging. (A) fluorescence images of Hep G2 and 4 T1 cells incubated with RdB/PEG-BPQDs. reprinted with permission from [57]. (B) In vitro imaging of 293 T cells treated with FA-PEG@BPQD@DOX and PEG@BPQD@DOX. (C) In vivo thermal images of mice with 293 T tumors irradiated at 808 nm. reprinted with permission from [58].

Advertisement

6. A brief comparison between carbon-based QDs and BPQDs

Carbon-based QDs and BPQDs both consist of only one type of element (carbon and phosphorus) and comparing their efficiency in cancer cell imaging can be very important. The results of various studies have shown that both types of quantum dots have a high ability in cancer cells imaging [73, 74]. However, concentrations of BPQDs used for cancer cell imaging are lower than carbon-based QDs [74, 75]. In this context, two hypothesis are raised: First, it is likely that BPQDs increase the intensity of the PL signal to a greater extent than carbon-based QDs. Second, the cytotoxicity of BPQDs is higher than that of carbon-based QDs, and they should be used in low concentrations. However, due to the few studies, especially on BPQDs, these two hypotheses cannot be decisive, and the need for more studies in this field will help to clarify the issue more.

Advertisement

7. Conclusion

In this chapter, various QDs were introduced and in addition to expressing methods of synthesis, modification and cytotoxicity, the bioimaging applications (in vitro and in vivo) were discussed. SQDs due to having heavy metal cannot be used for clinical application. But, nontoxic CuInS2 QDs are suitable alternatives for SQDs in biological imaging. Beside these QDs, carbon-based QDs, MoS2 QDs, and BP QDs have low toxicity and fluorescence emission in the NIR region of the light spectrum. The easy synthesis and the possibility of modification are other advantages of these QDs compared to SQDs. However, since studies have shown that QDs are not toxic at low concentrations, more research is needed to evaluate their blood circulation, cytotoxicity, etc. for bioimaging application. In addition, different methods of synthesis and modifications may affect the optical properties as well as the biocompatibility of QDs, and for this reason, more investigations should be done in this field. In the end, it should be noted that the use of safe QDs in clinical imaging techniques such as CT and MRI seems very likely in the near future.

Advertisement

Conflicts of interest

There are no conflicts to declare.

References

  1. 1. Fitzmaurice C et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncology. 2017;3(4):524-548
  2. 2. McHugh KJ et al. Biocompatible semiconductor quantum dots as cancer imaging agents. Advanced Materials. 2018;30(18):1706356
  3. 3. Alshehri S et al. Progress of cancer nanotechnology as diagnostics, therapeutics, and theranostics nanomedicine: Preclinical promise and translational challenges. Pharmaceutics. 2020;13(1):24
  4. 4. Smith RA et al. Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening. A Cancer Journal for Clinicians. 2018;68(4):297-316
  5. 5. Khaledian S et al. Applications of novel quantum dots derived from layered materials in cancer cell imaging. FlatChem. 2021;27:100246
  6. 6. Kubota SI et al. Whole-body profiling of cancer metastasis with single-cell resolution. Cell Reports. 2017;20(1):236-250
  7. 7. James ML, Gambhir SS. A molecular imaging primer: Modalities, imaging agents, and applications. Physiological Reviews. 2012;92(2):897-965
  8. 8. Alivisatos AP. Semiconductor clusters, nanocrystals, and quantum dots. Science. 1996;271(5251):933-937
  9. 9. Chen H et al. Quantum dots-enhanced chemiluminescence: Mechanism and application. Coordination Chemistry Reviews. 2014;263:86-100
  10. 10. Mason EA, Lopez R, Mason RP. Wavelength shifting of chemiluminescence using quantum dots to enhance tissue light penetration. Optical Materials Express. 2016;6(4):1384-1392
  11. 11. Nurunnabi M et al. In vivo biodistribution and toxicology of carboxylated graphene quantum dots. ACS Nano. 2013;7(8):6858-6867
  12. 12. Shao L, Gao Y, Yan F. Semiconductor quantum dots for biomedicial applications. Sensors. 2011;11(12):11736-11751
  13. 13. Chung S, Revia RA, Zhang M. Graphene quantum dots and their applications in bioimaging, biosensing, and therapy. Advanced Materials. 2021;33(22):1904362
  14. 14. Fan H y, et al. Graphene quantum dots (GQDs)-based nanomaterials for improving photodynamic therapy in cancer treatment. European Journal of Medicinal Chemistry. 2019;182:111620
  15. 15. Pandey S, Bodas D. High-quality quantum dots for multiplexed bioimaging: A critical review. Advances in Colloid and Interface Science. 2020;278:102137
  16. 16. Nair A et al. Natural carbon-based quantum dots and their applications in drug delivery: A review. Biomedicine & Pharmacotherapy. 2020;132:110834
  17. 17. Madani SY et al. Conjugation of quantum dots on carbon nanotubes for medical diagnosis and treatment. International Journal of Nanomedicine. 2013;8:941
  18. 18. Zhou W, Coleman JJ. Semiconductor quantum dots. Current Opinion in Solid State and Materials Science. 2016;20(6):352-360
  19. 19. García de Arquer FP et al. Semiconductor quantum dots: Technological progress and future challenges. Science. 2021;373(6555):eaaz8541
  20. 20. Gidwani B et al. Quantum dots: Prospectives, toxicity, advances and applications. Journal of Drug Delivery Science and Technology. 2021;61:102308
  21. 21. Parani S, Lakshmi BS, Pandian K. Biopolymer encapsulation of CdTe quantum dot for In vitro controlled drug delivery release of 6-mercaptopurine. In: Advanced Materials Research. Trans Tech Publications Ltd. 2012;584:258-262
  22. 22. Kang B et al. Synthesis of green CdSe/chitosan quantum dots using a polymer-assisted γ-radiation route. Radiation Physics and Chemistry. 2008;77(7):859-863
  23. 23. Chen X et al. Microwave-assisted synthesis of glutathione-capped CdTe/CdSe near-infrared quantum dots for cell imaging. International Journal of Molecular Sciences. 2015;16(5):11500-11508
  24. 24. Wang L et al. Semiconducting quantum dots: Modification and applications in biomedical science. Science China Materials. 2020;63(9):1631-1650
  25. 25. Xu Q et al. Quantum dots in cell imaging and their safety issues. Journal of Materials Chemistry B. 2021;9(29):5765-5779
  26. 26. Gao X et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nature Biotechnology. 2004;22(8):969-976
  27. 27. Parak WJ, Pellegrino T, Plank C. Labelling of cells with quantum dots. Nanotechnology. 2005;16(2):R9
  28. 28. Liu Z et al. Facile construction of near infrared fluorescence nanoprobe with amphiphilic protein-polymer bioconjugate for targeted cell imaging. ACS Applied Materials & Interfaces. 2015;7(34):18997-19005
  29. 29. Kim E-M et al. Facile synthesis of near-infrared CuInS2/ZnS quantum dots and glycol-chitosan coating for in vivo imaging. Journal of Nanoparticle Research. 2017;19(7):1-12
  30. 30. Zhao C et al. Small GSH-capped CuInS2 quantum dots: MPA-assisted aqueous phase transfer and bioimaging applications. ACS Applied Materials & Interfaces. 2015;7(32):17623-17629
  31. 31. Kays JC et al. Shell-free copper indium sulfide quantum dots induce toxicity in vitro and in vivo. Nano Letters. 2020;20(3):1980-1991
  32. 32. Xu X et al. Electrophoretic analysis and purification of fluorescent single-walled carbon nanotube fragments. Journal of the American Chemical Society. 2004;126(40):12736-12737
  33. 33. Li H et al. Water-soluble fluorescent carbon quantum dots and photocatalyst design. Angewandte Chemie International Edition. 2010;49(26):4430-4434
  34. 34. Zaini MS et al. Quantum confinement effect and photoenhancement of photoluminescence of PbS and PbS/MnS quantum dots. Applied Sciences. 2020;10(18):6282
  35. 35. Kim S et al. Anomalous behaviors of visible luminescence from graphene quantum dots: Interplay between size and shape. ACS Nano. 2012;6(9):8203-8208
  36. 36. Zhu S et al. Photoluminescence mechanism in graphene quantum dots: Quantum confinement effect and surface/edge state. Nano Today. 2017;13:10-14
  37. 37. Yang S et al. Large-scale fabrication of heavy doped carbon quantum dots with tunable-photoluminescence and sensitive fluorescence detection. Journal of Materials Chemistry A. 2014;2(23):8660-8667
  38. 38. Khaledian S et al. Rapid detection of diazinon as an organophosphorus poison in real samples using fluorescence carbon dots. Inorganic Chemistry Communications. 2021;130:108676
  39. 39. Zhu S et al. Highly photoluminescent carbon dots for multicolor patterning, sensors, and bioimaging. Angewandte Chemie. 2013;125(14):4045-4049
  40. 40. Tajik S et al. Carbon and graphene quantum dots: A review on syntheses, characterization, biological and sensing applications for neurotransmitter determination. RSC Advances. 2020;10(26):15406-15429
  41. 41. Wu X et al. Fabrication of highly fluorescent graphene quantum dots using L-glutamic acid for in vitro/in vivo imaging and sensing. Journal of Materials Chemistry C. 2013;1(31):4676-4684
  42. 42. Molaei MJ. Carbon quantum dots and their biomedical and therapeutic applications: A review. RSC Advances. 2019;9(12):6460-6481
  43. 43. Farshbaf M et al. Carbon quantum dots: Recent progresses on synthesis, surface modification and applications. Artificial Cells, Nanomedicine, and Biotechnology. 2018;46(7):1331-1348
  44. 44. Zou W-S et al. Insecticide as a precursor to prepare highly bright carbon dots for patterns printing and bioimaging: A new pathway for making poison profitable. Chemical Engineering Journal. 2016;294:323-332
  45. 45. Li K et al. Recent advances in the cancer bioimaging with graphene quantum dots. Current Medicinal Chemistry. 2018;25(25):2876-2893
  46. 46. Jiang D et al. Synthesis of luminescent graphene quantum dots with high quantum yield and their toxicity study. PLoS One. 2015;10(12):e0144906
  47. 47. Wang Y et al. Direct solvent-derived polymer-coated nitrogen-doped carbon nanodots with high water solubility for targeted fluorescence imaging of glioma. Small. 2015;11(29):3575-3581
  48. 48. Li S et al. Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids. Nature Biomedical Engineering. 2020;4(7):704-716
  49. 49. Lu H et al. Graphene quantum dots for optical bioimaging. Small. 2019;15(36):1902136
  50. 50. Wang X et al. Multifunctional graphene quantum dots for simultaneous targeted cellular imaging and drug delivery. Colloids and Surfaces B: Biointerfaces. 2014;122:638-644
  51. 51. Abdoli M et al. Polyvinyl alcohol/gum tragacanth/graphene oxide composite nanofiber for antibiotic delivery. Journal of Drug Delivery Science and Technology. 2020;60:102044
  52. 52. Khaledian S et al. Two-dimensional nanostructure colloids in novel nano drug delivery systems. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2020;585:124077
  53. 53. Khaledian S et al. Electrospun nanofiber patch based on gum tragacanth/polyvinyl alcohol/molybdenum disulfide composite for tetracycline delivery and their inhibitory effect on Gram+ and Gram-bacteria. Journal of Molecular Liquids. 2021;334:115989
  54. 54. Liu J et al. Multifunctional MoS2 composite nanomaterials for drug delivery and synergistic photothermal therapy in cancer treatment. Ceramics International. 1 Aug 2022;48(15): 22419-22427
  55. 55. Zhang W et al. Tumor acidity and near-infrared light responsive drug delivery MoS2-based nanoparticles for chemo-photothermal therapy. Photodiagnosis and Photodynamic Therapy. 2022;38:102716
  56. 56. Peng Y et al. Determination of folic acid via its quenching effect on the fluorescence of MoS2 quantum dots. Microchimica Acta. 2019;186(9):1-8
  57. 57. Li L et al. Facile synthesis of MoS 2 quantum dots as fluorescent probes for sensing of hydroquinone and bioimaging. Analytical Methods. 2019;11(26):3307-3313
  58. 58. Roy S et al. Targeted bioimaging of cancer cells using free folic acid-sensitive molybdenum disulfide quantum dots through fluorescence “turn-off”. ACS Applied Bio Materials. 2021;4(3):2839-2849
  59. 59. Liu Q , Hu C, Wang X. A facile one-step method to produce MoS 2 quantum dots as promising bio-imaging materials. RSC Advances. 2016;6(30):25605-25610
  60. 60. Shi M et al. “Bottom-up” preparation of MoS2 quantum dots for tumor imaging and their in vivo behavior study. Biochemical and Biophysical Research Communications. 2019;516(4):1090-1096
  61. 61. Zou B et al. Photothermal-healing, and record thermal stability and fire safety black phosphorus–boron hybrid nanocomposites: Mechanism of phosphorus fixation effects and charring inspired by cell walls. Journal of Materials Chemistry A. 2022;10(27):14423-14434
  62. 62. Tao W et al. Black phosphorus nanosheets as a robust delivery platform for cancer theranostics. Advanced Materials. 2017;29(1):1603276
  63. 63. Qiu M et al. Biocompatible and biodegradable inorganic nanostructures for nanomedicine: Silicon and black phosphorus. Nano Today. 2019;25:135-155
  64. 64. Shao J et al. Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy. Nature Communications. 2016;7(1):1-13
  65. 65. Zhang W et al. Phycocyanin-functionalized black phosphorus quantum dots enhance PDT/PTT therapy by inducing ROS and irreparable DNA damage. Biomaterials Science. 2021;9(15):5302-5318
  66. 66. Liu J et al. Dual-triggered oxygen self-supply black phosphorus nanosystem for enhanced photodynamic therapy. Biomaterials. 2018;172:83-91
  67. 67. Qi F et al. Photosynthetic cyanobacteria-hybridized black phosphorus nanosheets for enhanced tumor photodynamic therapy. Small. 2021;17(42):2102113
  68. 68. Chen H et al. Nanocomposite of Au and black phosphorus quantum dots as versatile probes for amphibious SERS spectroscopy, 3D photoacoustic imaging and cancer therapy. Giant. 2021;8:100073
  69. 69. Gui R et al. Black phosphorus quantum dots: Synthesis, properties, functionalized modification and applications. Chemical Society Reviews. 2018;47(17):6795-6823
  70. 70. Ding H et al. Black phosphorus quantum dots as multifunctional nanozymes for tumor photothermal/catalytic synergistic therapy. Nano Research. 2022;15(2):1554-1563
  71. 71. Li Y et al. Multifunctional nanoplatform based on black phosphorus quantum dots for bioimaging and photodynamic/photothermal synergistic cancer therapy. ACS Applied Materials & Interfaces. 2017;9(30):25098-25106
  72. 72. Wang J et al. PEGylated-folic acid–modified black phosphorus quantum dots as near-infrared agents for dual-modality imaging-guided selective cancer cell destruction. Nano. 2020;9(8):2425-2435
  73. 73. Chen H et al. Ultra-stable tellurium-doped carbon quantum dots for cell protection and near-infrared photodynamic application. Science Bulletin. 2020;65(18):1580-1586
  74. 74. Li Z et al. Polydopamine-functionalized black phosphorus quantum dots for cancer theranostics. Applied Materials Today. 2019;15:297-304
  75. 75. Bouzas-Ramos D et al. Carbon quantum dots codoped with nitrogen and lanthanides for multimodal imaging. Advanced Functional Materials. 2019;29(38):1903884

Written By

Salar Khaledian, Mohadese Abdoli, Reza Fatahian and Saleh Salehi Zahabi

Submitted: 02 August 2022 Reviewed: 02 September 2022 Published: 20 January 2023