The recent advances in nanoscience and technology have opened new avenues for carbon-based nanomaterials. Especially, Carbon dots (CDs) have gained significant attention due to their simple, economic and rapid green synthesis. These materials exhibit excellent water solubility, fluorescence emission, high fluorescence quantum yield, Ultraviolet (UV) to Infrared (IR) range absorbance and high bio-compatibility. Therefore, these materials are widely used for various biological applications including bio-imaging. With the integration and doping of surface passive agents and elements, respectively influenced the enhancement of fluorescence property of CDs. Also, the conjugation of receptor-based targeting ligands leads to targeted bioimaging. CDs in combination with other imaging contrast agents lead to the development of novel contrast agents for bimodal imaging and multimodal imaging techniques. The combination of diagnostic CDs with therapeutic agents resulted in the formation of theragnostic CDs for image guided therapies. In this chapter, a comprehensive view on the top-down and bottom–up green synthesis methods for naturally derived CDs discussed. Further, unique physical, chemical, optical and biological properties of CDs described. Finally, fluorescence based bimodal and multimodal imaging techniques also described.
- carbon dot
- contrast agent
The term ‘imaging’ is a perception that it is a type of photography; however, it is far from the biomedical domain. Bioimaging provides the anatomical visualization of cellular, subcellular structures, tissues, organs of multicellular organisms . The biomedical imaging modalities utilize the various kind of energy sources such as light, magnetic resonance, positrons, ultrasound, electrons, and X-rays. The broad range of medical imaging modalities includes fluorescence (FL); X-ray computed tomography (CT), magnetic resonance (MR), ultrasound (US), positron emission tomography (PET) and single-photon emission computed tomography (SPECT) for diagnosis of various soft tissues and hard tissue pathologies and scientific research . These techniques disclose the three-dimensional molecular information of any specimen’s biological structures and physiological processes.
Optical imaging, predominantly FL imaging modality received special attention from all the imaging modalities due to their simple operation process, cost-effective armamentarium, excellent resolution, incredible sensitivity and high resolution [3, 4, 5]. Therefore, a wide range of fluorescent imaging probes has been discovered for FL imaging, such as organic dyes, semiconductor quantum dots, metal nanocluster and up-conversion nanoparticles [3, 4, 6]. Nevertheless, their limitations include high toxicity, complicated synthesis mechanisms, poor water-solubility and high cost. On the other hand, single-mode fluorescence imaging techniques were limited to depth penetration and difficulty to provide tomographic information due to light attenuation and photon scattering of biological tissue. Therefore, developing FL based multimodal imaging by integrating other imaging modalities with FL imaging modality has become an essential strategy to resolve the single mode FL imaging limitations. Interestingly, FL based multimodal imaging provides several advantages including non-invasive imaging visualization with superior depth penetration, higher sensitivity and resolution . Hence, it is necessary to develop a single probe by integrating other contrast agents with fluorescent materials for FL-based multimodality imaging applications.
Nanotechnology advancements in contrast agent development are progressing rapidly either by doping/incorporating or conjugation of other contrast elements into/with fluorescent nanomaterials to obtain a multimodal imaging probe . Among the various types of nanomaterials, carbon dots (CDs) gained remarkable attention due to their significant physical, chemical and biological properties . The integration of several unique properties in single nanosize carbon dots (CDs), make them ideal alternative material to replace the semiconductor quantum dots, metallic nanomaterials and other forms of carbon materials in various fields. Specifically, bioimaging, drug delivery, phototherapy, anti-microbial agents, sensors, solar cells, light-emitting diodes and photocatalysis [10, 11, 12, 13]. Specifically, CDs show significant potential in fluorescence-based multimodal imaging
2. Synthesis methods of carbon dots
In 2004, during the purification process of single-walled carbon nanotubes (SWCNTs) using gel electrophoresis, the CDs were discovered . Later, various procedures established for the synthesis of CDs. Broadly, the CDs synthesis methods can be classified into as “top-down” and “bottom-up” approaches (Figure 1).
2.1 Top-down method
In the “top-down” approach, the breakdown of bulk carbon materials into nano size carbon occurs under relatively harsh conditions such as oxidative acid treatment, electrochemical exfoliation, laser ablation, and arc discharge . The first described CDs were produced by the top-down process via laser ablation of graphite in the gaseous phase, subsequently acid oxidative treatment . Later, numerous methods such as arc discharge, etching, electrochemical oxidation, ultrasonication, chemical exfoliation, and nitric acid/sulfuric acid oxidation developed to obtained CDs by reducing the size of bulk carbon materials [14, 16]. Mostly, graphite, graphene or graphene oxide (GO) sheets, carbon nanotubes (CNTs), carbon fibers and carbon soot etc. used as a precursor material in these methods. Even though these methods were successfully used to prepare CDs, they are limited with harsh conditions, complicated synthesis strategies, low quantum yield, expensive, eco-unfriendly, and unsuitable for the production of CDs in industrial-scale. These methods rarely used for the preparation of CDs from natural sources.
2.1.1 Bottom-up method
In the “bottom-up” approach, the CDs are synthesized from carbon-containing small molecules in a “polymerization– carbonization” process. Several methods include combustion, hydrothermal, solvothermal, and microwave-assisted pyrolysis developed in bottom-up synthesis . Typically, in these methods carbon precursor such as small organic molecules taken in a liquid or gas stage are ionized, dissociated, sublimated or evaporated and then condensed via condensation, carbonization, polymerization and passivation to form nanosize CDs. Compared with the “top-down” strategy, the “bottom-up” approach is extensively used for the green synthesis of CDs using natural renewable sources. Here, we discussed some important synthesis methods of CDs.
2.1.2 Natural materials as a green precursor for preparation of CDs
The green synthesis of CDs relies on natural precursors such as plant materials, protein products and waste materials . Compared with bulk carbon materials (Graphene, Graphene Oxide and carbon tubes etc.) and toxic organic compounds including aromatic molecules, natural materials are renewable, economical, eco-friendly, safer and easier to get industrial-scale production. Mostly, “bottom-up” methods adopted for the synthesis of CDs due to the existing small organic molecules in natural sources can be carbonized into CDs at a specific temperature. A few top-down methods developed for the waste bulk carbon materials or bio-waste are broken down/cut into small-sized CDs. Among the various techniques, hydrothermal and microwave approaches are extensively used to prepare CDs from multiple natural materials. Most natural sources or biomass materials are made with small organic molecules, converted into CDs by carbonization and pyrolysis.
In recent years, various kind of plant material such as coriander leaves, ginger, garlic, grass, coffee beans, lemon, orange juice etc. due to the existence of various carbon containing organic molecules including carbohydrates, cellulose and phenolic compounds . Compared with commercial precursors, the plant material derived CDs showed enhanced fluorescence emission with high quantum yield due to heteroatoms such as nitrogen, sulfur and phosphorus. Hence, the optical and structural properties of CDs are mainly relying on the selection of natural precursors. Besides this, with the growing concern about environmental pollution and sustainability, variety of waste materials including different kind of agriculture, kitchen, fruit peel and seafood waste etc. used as a starting material for the preparation of CDs [30, 42, 43]. These waste resources, also containing organic molecules, can be polymerized and followed by carbonized to form CDs.
2.2 General properties
The general properties of CDs illustrated in Figure 2. Structurally, CDs belongs to the quasi-spherical zero-dimension carbon nanomaterials class with a size of less than 10 nm [44, 45]. They are amorphous or nanocrystalline cores with a typical sp2 carbon hybridization. The absorption band of CDs exhibits UV–Visible region to the NIR region and contains various functional groups. The electrifying properties of CDs are their excitation wavelength-dependent emission spectrum, high photostability and resisting to photobleaching, which permits CDs for multicolour and long-term imaging applications, respectively . The cytotoxicity and preclinical biocompatibility of CDs on various models such as cell lines, zebrafish, mice displayed CDs have no apparent toxic effects. Extensive studies are to be done on the toxicological and biocompatibility properties to translate from preclinical to clinical application. For targeted bio-imaging, the surface functional groups such as hydroxyl, amine and carboxylic groups allow conjugation with targeting agents.
2.2.1 Optical properties
Among all the CDs’ properties, optical properties such as absorbance and fluorescence are vital for bio-imaging applications [45, 46]. Usually, CDs exhibited a strong absorption band at UV region with a falling intensity absorption tail increased to the visible light region. Usually, absorption peak around 230–340 nm was typically ascribed due to π-π* transition of the C=C bonds of the carbon core. Similarly, the absorption band of 350–550 nm is ascribed to the surface functional groups on the carbon core. Besides this, one exciting feature of CDs is their excitation wavelength-dependent emission spectrum by varying excitation light wavelength, which is commonly observed in most CDs, which allows for multicolour imaging applications. CDs’ exact PL mechanism is currently debatable due to the various methods available for the preparation of CDs and the lack of consistency in CDs’ PL behavior. Nevertheless, three main mechanisms have been proposed to explain the PL of CDs: (1) The intrinsic band gap arising from the quantum confinement effect or the conjugated π domains, determined by CDs carbon core. (2) The creation of trap states (such as surface defects) in the band gap due to the surface functionalization and CDs doping. (3) The presence of individual fluorescent molecules (fluorophores) on or within the CDs. According to these theories, the wide tunable emissions of CDs have been attributed to their broad size distribution, variable surface chemistry, and the uncontrolled preparation conditions. Another fascinating PL property about CDs is that they generally exhibit high photostability, resisting photobleaching, which is very important for long-term imaging applications.
2.2.2 Elemental doping and surface functionalization
Usually, most of the bare CDs showed comparatively weak FL ability than traditional semiconductor quantum dots or organic dyes. In this line, CDs’ structure altered by incorporating elements or surface functionalization strategies to improve fluorescence properties which are essential for fluorescence-based bio-imaging applications. So far, a variety of element doping is adopted to obtain CDs with charming FL properties. At present, heteroatoms such as N, S, Si, P, B, Ga, halogen (Cl, Br, I), Se, Ge, Mg, Cu, Zn, Tb, Ru and Mn incorporated into CDs during the synthesis process [47, 48]. Besides this, large functional groups such as carboxylic acid, amine, hydroxyl and amide groups presence on the surface of CDs facilitate the opportunity to conjugate with various passivate agents [38, 49]. Therefore, several groups focused on improving the fluorescence efficiency through conjugation with variety of passivating agents such as Polyethylene glycol, polyethyleneimine, poly (propionyl ethyleneimine co-ethyleneimine), 4,7,10-trioxa-1,13-tridecanediamine, 1-hexadecylamine, poly(ethylenimide)-b-poly(ethyleneglycol)-b-poly (ethylene imide) and amino acids etc. Generally, these passivating conjugate with CDs via electrostatic interactions, covalent bonds, and hydrogen bonds. More interestingly hetero element doped or surface modified CDs also improved water solubility, photostability, biocompatibility, NIR absorbance and multicolour fluorescence emission, which are the vital parameters for bioimaging. Moreover, unique surface functional CDs have been prepared based on individual cell membrane lipids, proteins, targeting ligands and biomarkers of different cells to develop impactful imaging applications. Furthermore, variety of targeting moieties including peptides (transferrin), aptamers, antibodies and small molecules (folic acid) which have been selected to integrate on the surface of CD through N-hydroxy succinimide (NHS) or 1- ethyl-3-(3-dimethyl-aminopropyl) carbodiimide hydro-chloride (EDC) chemistry . These targeting moieties offer the internalization of CDs into cells or tissues via a ligand-receptor interaction. Remarkable specific cell targeting bioimaging besides adequate circulation of CDs avoid the side effects originating from the nonspecific interactions. The targeting moiety linked to CDs improves the specificity of bioimaging. Moreover, various cancer therapeutic drugs, anti-microbial agents and photosensitizers were conjugated with the CDs’ surface for image guided therapeutic applications.
Bioimaging is an emerging field of biomedical science that comprises of the development and application of various materials for imaging technologies [51, 52]. The bioimaging techniques principles are mainly based on optics, magnetic resonance, nuclear medicine, radiation, ultrasonics, photonics and spectroscopy. The anatomical and physiological quantification of clinical parameters is measured with the image processing and analysis. With the recent development of biomedical science and emerging newer technologies, the
4. Importance of carbon dot in bio-imaging
For clinical imaging application, good biocompatibility and low cytotoxicity of imaging probes are essential. The traditional quantum dots (QDs) such as CdSe, CdTe, CdS, and PbS were applied in
4.1 Fluorescence imaging
FL imaging is a promising technique for observing and assessing various cells, tissues and organisms, by the high fluorescence emission with biocompatible fluorescent agents [56, 57]. Currently, fluorescent CDs are considered as a significant alternative ideal contrast agent for fluorescence imaging. Several reports revealed that cells incubated with CDs emitted fluorescence mainly due to accumulation of CDs in the cells. Generally, unmodified/bare CDs are majorly identified in the cell membrane and cytoplasmic region without reaching the nuclei. To resolve this issue, excessive effort have been devoted to surface modify the CDs with targeting agents including antibodies, peptides and other biomolecules to enhance the specific targeted bioimaging. These target ligands modified CDs showed a significant capacity to bind to the overexpressed reprehensive receptor/biomarker on cells. In addition, to resolve the issues related to deep tissue fluorescence imaging, the NIR receptive CDs were designed with longer excitation/emission wavelengths that enhanced fluorescence imaging ability  for
4.2 Multimodal imaging
Every imaging technique has its unique advantages in consort with integral limitations such as insufficient sensitivity or spatial resolution (Figure 4) . Even the fluorescence imaging provides high sensitivity but lacks of sufficient resolution. To compensate this drawback, the combination of fluorescence imaging techniques with other modalities, such as FL/MRI has gained attention to enhance the currently used imaging techniques for diagnosis . Multimodal imaging is a combination of two or more imaging techniques to overcome individual limitations. The development of multi-modality imaging with the FL imaging is to achieve non-invasive imaging at greater depths of penetration, sensitivity and higher resolution required for an accurate diagnosis. Thus, optical imaging assisted multi-modalities has emerged as potent tools, which can improve the detection sensitivity, precise identification and provide more detailed anatomical or biological information of the pathology. Each imaging technique uses different contrast agents with distinctive functional, chemical compositions and sizes. In designing and developing a multi modal contrast agent, the researchers should judiciously forbid the overlay of pros and somewhat counterbalance each modality’s limitations to enhance the synergistic effect. Thus, the FL imaging modality with high sensitivity is frequently combined with other imaging modalities with a high spatial resolution modality such as MR, CT, and PA etc. (Figure 5). Hence, multimodal contrast agents’ development and application are clinically significant for enhanced imagery from desirable imaging modality. Multimodal imaging agents based on fluorescent CDs are the recent cutting-edge technologies where CDs’ advantages are maximized. CDs based multimodal imaging agents are prepared by conjugating or incorporating one or more imaging agents into CDs. Here we have discussed various kinds of fluorescent CDs’ based multi-modality imaging approaches such as FL/PA, FL/MR and FL/CT imaging.
4.2.1 Fluorescence/photoacoustic imaging
Photoacoustic (PA) imaging is a non-invasive, hybrid, optical and ultrasound imaging modality. The PA imaging is performed at varying depths with high depth to resolution ratio with rich optical contrast beyond the optical detection limit. The CDs have shown significant PA imaging application because of the NIR absorption, high extinction coefficient, and non-radiative heat generation. Wang,
4.2.2 Fluorescence/magnetic resonance imaging
Magnetic resonance imaging (MRI), is a radiation-free and non-invasive imaging technique widely used to detect various diseases including clinical cancer diagnosis and therapeutic response assessment . With an external radiofrequency pulse magnetic field applied on the body, it simultaneously obtains anatomical and physiological information of regions of interests with a high spatial resolution by manipulating magnetic nucleus’s resonance (1H). Further, the integration of FL imaging with MR imaging considered as most effective non-invasive imaging tool in diagnosis and clinical research due its excellent spatial resolution, high temporal and sensitivity. Hence, the CDs assisted FL/MR dual modality potentiality can take benefits of the spatial resolution, outstanding soft-tissue contrast with MR imaging as well as superior sensitivity and the rapid data acquiring with FL imaging. This dual imaging modality is facilitated precise diagnosis with effective treatment based on corresponding imaging evidence. The CDs-relayed FL/MR dual-mode imaging modality probe can be obtained by the doping/ conjugation of magnetic elements. Specifically, extremely paramagnetic ions including Gd3+, Mn2+, and Fe3+ employed as dopant for the preparation of FL/MR bimodal contrast agent such as Gd or Mn elements into CDs. For example, Gd3+ doped CDs were synthesized from Gd3+ containing precursors and sucrose as carbon precursors via microwave assisted method polyol by Gong Ningqiang,
Further, Jia Qingyan,
4.2.3 Fluorescence/X-ray computed tomography
X-ray computed tomography (CT) is a non-invasive medical imaging technique for disease diagnosis. The CT has intrinsic advantages such as high spatial resolution and good density; it still has inherent drawbacks of low sensitivity. On the other hand, the fluorescence imaging has high sensitivity, facile operation and low cost, but its application was hampered due to the low spatial resolution and limited penetration depth. To improve clinical diagnostic accuracy and sensitivity, the FL and CT imaging are combined for a synergistic effect. The CDs doped with Hafnium (Hf) was used for diagnostic imaging of the orthotopic liver cancer preclinical model . Rapid imaging was achieved with Hafnium doped CDs due to preferential tumor accumulation within 1 min. These imaging nanoprobes with efficient renal clearance offers good biocompatibility. Iodine doped CDs conjugated with a chemotherapeutic agent like cetuximab simultaneously rendered the cancer diagnosis and targeted anti-cancer therapeutic potential in lung cancer cells .
5. Imaging guided therapeutic application
Nanotechnology provides the possibility of developing non-toxic CDs nanoprobes with enhanced sensitivity, accuracy and advanced functionalities for imaging-guided synergistic therapy [69, 70]. The unique advantages of CDs include high relaxivity, prolonged blood circulation time, multiple functionalities for accurate accumulation in the target site, good biocompatibility and renal clearance. The inherent radio resistance of tumors and inaccurate positioning of the radiotherapeutic equipment leads to decreased radiotherapy effectiveness. Du Fengyi,
6. Conclusions and outlook
Naturally, renewable sources derived CDs are kind of newly born luminescent carbon-based nanomaterials in this decade. They gained great potential in bio-imaging not only because of their cost-effective and eco-friendly green synthetic approaches but also their physical, chemical and biological properties. We have elaborately discussed various synthesis methods, significant properties. Furthermore, the recent development of CD in multimodal bio-imaging. Their strong fluorescence emission, high fluorescent quantum yield, and good absorbance are widely used for fluorescence imaging. Specific CDs also allow for multicolour bioimaging due to their multicolour emission capability. Further, numerous surface functional groups provide an opportunity to conjugate with targeting moieties such folic acid for targeting imaging. Accordingly, CDs conjugation with targeted moieties can precisely transport imaging contrast agents to internal organelles or cell membranes to attain the goal of targeted bio-imaging. In the meantime, the large surface area of CDs permits them to have a more quantity of hetero atom loading ability, consequently showing remarkable multimodal imaging ability. Finally, the nano size of CDs (typically >10 nm) facilitates their navigation in tissues, endocytosis, and intracellular trafficking. Even though significant efforts have devoted to improving the multimodal imaging effect of CDs, several limitations hinder the application of CDs in bio-imaging. Primarily, the emission from most of the natural sources derived CDs showed blue or green, thus developing the methods and finding suitable natural precursor for yellow or red emissive CDs is highly desired. CDs exhibit excellent biocompatibility; however, majority studies are confined to cellular and preclinical experiments, but translation into clinical investigations is still unclear. In summary, more research still needs to be made for the effective and real-time clinical application of CDs in multimodal imaging.
T.-L. Liu, S. Upadhyayula, D.E. Milkie, V. Singh, K. Wang, I.A. Swinburne, K.R. Mosaliganti, Z.M. Collins, T.W. Hiscock, J. Shea, A.Q . Kohrman, T.N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E.M. Meyerowitz, D. Hockemeyer, D.G. Drubin, B.L. Martin, D.Q . Matus, M. Koyama, S.G. Megason, T. Kirchhausen, E. Betzig, Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms, Science 360(6386) (2018) eaaq1392
J. Kim, Y. Piao, T. Hyeon, Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy, Chemical Society Reviews 38(2) (2009) 372-390
J. Rao, A. Dragulescu-Andrasi, H. Yao, Fluorescence imaging in vivo: recent advances, Current opinion in biotechnology 18(1) (2007) 17-25
M. Schäferling, The art of fluorescence imaging with chemical sensors, Angewandte Chemie International Edition 51(15) (2012) 3532-3554
P.P. Laissue, R.A. Alghamdi, P. Tomancak, E.G. Reynaud, H. Shroff, Assessing phototoxicity in live fluorescence imaging, Nature methods 14(7) (2017) 657-661
X. Li, L. Que, Fluorescence Enhancement Enabled by Nanomaterials and Nanostructured Substrates: A Brief Review, Reviews in Nanoscience and Nanotechnology 3(3) (2014) 161-176
J. Zhao, J. Chen, S. Ma, Q . Liu, L. Huang, X. Chen, K. Lou, W. Wang, Recent developments in multimodality fluorescence imaging probes, Acta Pharmaceutica Sinica B 8(3) (2018) 320-338
Z. Liu, F. Kiessling, J. Gätjens, Advanced Nanomaterials in Multimodal Imaging: Design, Functionalization, and Biomedical Applications, Journal of Nanomaterials 2010 (2010) 894303
J. Wang, J. Qiu, A review of carbon dots in biological applications, Journal of Materials Science 51(10) (2016) 4728-4738
P. Zuo, X. Lu, Z. Sun, Y. Guo, H. He, A review on syntheses, properties, characterization and bioanalytical applications of fluorescent carbon dots, Microchimica Acta 183(2) (2016) 519-542
J. Zuo, T. Jiang, X. Zhao, X. Xiong, S. Xiao, Z. Zhu, Preparation and application of fluorescent carbon dots, Journal of Nanomaterials 2015 (2015)
X. Zhang, Q . Zeng, Y. Xiong, T. Ji, C. Wang, X. Shen, M. Lu, H. Wang, S. Wen, Y. Zhang, Energy Level Modification with Carbon Dot Interlayers Enables Efficient Perovskite Solar Cells and Quantum Dot Based Light-Emitting Diodes, Advanced Functional Materials 30(11) (2020) 1910530
X. Dong, W. Liang, M.J. Meziani, Y.-P. Sun, L. Yang, Carbon dots as potent antimicrobial agents, Theranostics 10(2) (2020) 671
J.-H. Qu, Q . Wei, D.-W. Sun, Carbon dots: Principles and their applications in food quality and safety detection, Critical reviews in food science and nutrition 58(14) (2018) 2466-2475
L.S. Chu K-W, Chang C-J, Liu L. Recent Progress of Carbon Dot Precursors and Photocatalysis Applications., Polymers (Basel) 11(4):689 (2019)
R. Jelinek, Carbon-Dot Synthesis, Carbon Quantum Dots: Synthesis, Properties and Applications, Springer International Publishing, Cham, 2017, pp. 5-27
J.C.E. da Silva, H.M. Gonçalves, Analytical and bioanalytical applications of carbon dots, TrAC Trends in Analytical Chemistry 30(8) (2011) 1327-1336
V. Mishra, A. Patil, S. Thakur, P. Kesharwani, Carbon dots: emerging theranostic nanoarchitectures, Drug discovery today 23(6) (2018) 1219-1232
Z.-A. Qiao, Y. Wang, Y. Gao, H. Li, T. Dai, Y. Liu, Q . Huo, Commercially activated carbon as the source for producing multicolor photoluminescent carbon dots by chemical oxidation, Chemical Communications 46(46) (2010) 8812-8814
J. Joseph, A.A. Anappara, White-Light-Emitting Carbon Dots Prepared by the Electrochemical Exfoliation of Graphite, ChemPhysChem 18(3) (2017) 292-298
X. Li, Z. Zhao, C. Pan, Electrochemical exfoliation of carbon dots with the narrowest full width at half maximum in their fluorescence spectra in the ultraviolet region using only water as electrolyte, Chemical Communications 52(60) (2016) 9406-9409
X. Li, Z. Zhao, C. Pan, Ionic liquid-assisted electrochemical exfoliation of carbon dots of different size for fluorescent imaging of bacteria by tuning the water fraction in electrolyte, Microchimica Acta 183(9) (2016) 2525-2532
D. Reyes, M. Camacho, M. Camacho, M. Mayorga, D. Weathers, G. Salamo, Z. Wang, A. Neogi, Laser ablated carbon nanodots for light emission, Nanoscale research letters 11(1) (2016) 1-11
D. Reyes-Contreras, M. Camacho-López, M.A. Camacho-López, S. Camacho-López, R.I. Rodríguez-Beltrán, M. Mayorga-Rojas, Influence of the per pulse laser fluence on the optical properties of carbon nanoparticles synthesized by laser ablation of solids in liquids, Optics & Laser Technology 74 (2015) 48-52
K. Dehvari, K.Y. Liu, P.-J. Tseng, G. Gedda, W.M. Girma, J.-Y. Chang, Sonochemical-assisted green synthesis of nitrogen-doped carbon dots from crab shell as targeted nanoprobes for cell imaging, Journal of the Taiwan Institute of Chemical Engineers 95 (2019) 495-503
S.K. Das, R. Gawas, S. Chakrabarty, G. Harini, R. Patidar, K. Jasuja, An unexpected transformation of organic solvents into 2D fluorescent quantum dots during ultrasonication-assisted liquid-phase exfoliation, The Journal of Physical Chemistry C 123(41) (2019) 25412-25421
X. Zhai, P. Zhang, C. Liu, T. Bai, W. Li, L. Dai, W. Liu, Highly luminescent carbon nanodots by microwave-assisted pyrolysis, Chemical Communications 48(64) (2012) 7955-7957
V. Hinterberger, W. Wang, C. Damm, S. Wawra, M. Thoma, W. Peukert, Microwave-assisted one-step synthesis of white light-emitting carbon dot suspensions, Optical Materials 80 (2018) 110-119
A. Tangy, V.B. Kumar, I.N. Pulidindi, Y. Kinel-Tahan, Y. Yehoshua, A. Gedanken, In-situ transesterification of Chlorella vulgarisusing carbon-dot functionalized strontium oxide as a heterogeneous catalyst under microwave irradiation, Energy & Fuels 30(12) (2016) 10602-10610
H. Fan, M. Zhang, B. Bhandari, C.-h. Yang, Food waste as a carbon source in carbon quantum dots technology and their applications in food safety detection, Trends in Food Science & Technology 95 (2020) 86-96
A. Himaja, P.S. Karthik, B. Sreedhar, S.P. Singh, Synthesis of carbon dots from kitchen waste: conversion of waste to value added product, Journal of fluorescence 24(6) (2014) 1767-1773
X.W. Tan, A.N.B. Romainor, S.F. Chin, S.M. Ng, Carbon dots production via pyrolysis of sago waste as potential probe for metal ions sensing, Journal of analytical and applied pyrolysis 105 (2014) 157-165
J.-Y. Wan, Z. Yang, Z.-G. Liu, H.-X. Wang, Ionic liquid-assisted thermal decomposition synthesis of carbon dots and graphene-like carbon sheets for optoelectronic application, RSC advances 6(66) (2016) 61292-61300
A. Zheng, T. Guo, F. Guan, X. Chen, Y. Shu, J. Wang, Ionic liquid mediated carbon dots: Preparations, properties and applications, TrAC Trends in Analytical Chemistry 119 (2019) 115638
W. Shang, T. Cai, Y. Zhang, D. Liu, S. Liu, Facile one pot pyrolysis synthesis of carbon quantum dots and graphene oxide nanomaterials: all carbon hybrids as eco-environmental lubricants for low friction and remarkable wear-resistance, Tribology International 118 (2018) 373-380
M. Rong, Y. Feng, Y. Wang, X. Chen, One-pot solid phase pyrolysis synthesis of nitrogen-doped carbon dots for Fe3+ sensing and bioimaging, Sensors and Actuators B: Chemical 245 (2017) 868-874
C. Wang, Z. Xu, H. Cheng, H. Lin, M.G. Humphrey, C. Zhang, A hydrothermal route to water-stable luminescent carbon dots as nanosensors for pH and temperature, Carbon 82 (2015) 87-95
S. mitra, S. Chandra, S.H. Pathan, N. Sikdar, P. Pramanik, A. Goswami, Room temperature and solvothermal green synthesis of self passivated carbon quantum dots, RSC Advances 3(10) (2013) 3189-3193
M. Li, C. Yu, C. Hu, W. Yang, C. Zhao, S. Wang, M. Zhang, J. Zhao, X. Wang, J. Qiu, Solvothermal conversion of coal into nitrogen-doped carbon dots with singlet oxygen generation and high quantum yield, Chemical Engineering Journal 320 (2017) 570-575
X. Guo, H. Zhang, H. Sun, M.O. Tade, S. Wang, Green Synthesis of Carbon Quantum Dots for Sensitized Solar Cells, ChemPhotoChem 1(4) (2017) 116-119
A.H. Zulfajri M, Sudewi S, Dayalan S, Rasool A, Habib A, Huang GG. Plant Part-Derived Carbon Dots for Biosensing, Biosensors 10(6):68. (2020)
P. Kaur, S. Singh, G. Verma, Facile synthesis of mesoporous carbon material from treated kitchen waste for energy applications, Materials for Renewable and Sustainable Energy 7(2) (2018) 9
V. Sharma, P. Tiwari, S.M. Mobin, Sustainable carbon-dots: recent advances in green carbon dots for sensing and bioimaging, Journal of Materials Chemistry B 5(45) (2017) 8904-8924
X.T. Zheng, A. Ananthanarayanan, K.Q . Luo, P. Chen, Glowing Graphene Quantum Dots and Carbon Dots: Properties, Syntheses, and Biological Applications, Small 11(14) (2015) 1620-1636
M. Semeniuk, Z. Yi, V. Poursorkhabi, J. Tjong, S. Jaffer, Z.-H. Lu, M. Sain, Future Perspectives and Review on Organic Carbon Dots in Electronic Applications, ACS Nano 13(6) (2019) 6224-6255
P. Namdari, B. Negahdari, A. Eatemadi, Synthesis, properties and biomedical applications of carbon-based quantum dots: An updated review, Biomedicine & Pharmacotherapy 87 (2017) 209-222
Q . Xu, T. Kuang, Y. Liu, L. Cai, X. Peng, T. Sreenivasan Sreeprasad, P. Zhao, Z. Yu, N. Li, Heteroatom-doped carbon dots: synthesis, characterization, properties, photoluminescence mechanism and biological applications, Journal of Materials Chemistry B 4(45) (2016) 7204-7219
S. Miao, K. Liang, J. Zhu, B. Yang, D. Zhao, B. Kong, Hetero-atom-doped carbon dots: Doping strategies, properties and applications, Nano Today 33 (2020) 100879
J. Pan, Z. Zheng, J. Yang, Y. Wu, F. Lu, Y. Chen, W. Gao, A novel and sensitive fluorescence sensor for glutathione detection by controlling the surface passivation degree of carbon quantum dots, Talanta 166 (2017) 1-7
Y. Song, S. Zhu, B. Yang, Bioimaging based on fluorescent carbon dots, RSC Advances 4(52) (2014) 27184-27200
Q . Le Trequesser, H. Seznec, M.-H. Delville, Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches, Nanotechnology Reviews 2(2) (2013) 125-169
R. Bilan, I. Nabiev, A. Sukhanova, Quantum Dot-Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery, ChemBioChem 17(22) (2016) 2103-2114
I.L. Medintz, H.T. Uyeda, E.R. Goldman, H. Mattoussi, Quantum dot bioconjugates for imaging, labelling and sensing, Nature materials 4(6) (2005) 435-446
F. Erogbogbo, K.-T. Yong, I. Roy, G. Xu, P.N. Prasad, M.T. Swihart, Biocompatible luminescent silicon quantum dots for imaging of cancer cells, ACS nano 2(5) (2008) 873-878
Y.-C. Shiang, C.-C. Huang, W.-Y. Chen, P.-C. Chen, H.-T. Chang, Fluorescent gold and silver nanoclusters for the analysis of biopolymers and cell imaging, Journal of Materials Chemistry 22(26) (2012) 12972-12982
X. Wu, F. Tian, W. Wang, J. Chen, M. Wu, 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 1(31) (2013) 4676-4684
T.-s. Chu, R. Lü, B.-t. Liu, Reversibly monitoring oxidation and reduction events in living biological systems: recent development of redox-responsive reversible NIR biosensors and their applications in in vitro/in vivo fluorescence imaging, Biosensors and Bioelectronics 86 (2016) 643-655
J.H. Lee, Y.w. Jun, S.I. Yeon, J.S. Shin, J. Cheon, Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma, Angewandte Chemie International Edition 45(48) (2006) 8160-8162
D.-E. Lee, H. Koo, I.-C. Sun, J.H. Ryu, K. Kim, I.C. Kwon, Multifunctional nanoparticles for multimodal imaging and theragnosis, Chemical Society Reviews 41(7) (2012) 2656-2672
J. Ge, Q . Jia, W. Liu, L. Guo, Q . Liu, M. Lan, H. Zhang, X. Meng, P. Wang, Red-emissive carbon dots for fluorescent, photoacoustic, and thermal theranostics in living mice, Advanced Materials 27(28) (2015) 4169-4177
F. Wu, H. Su, Y. Cai, W.-K. Wong, W. Jiang, X. Zhu, Porphyrin-implanted carbon nanodots for photoacoustic imaging and in vivo breast cancer ablation, ACS Applied Bio Materials 1(1) (2018) 110-117
L. Wu, X. Cai, K. Nelson, W. Xing, J. Xia, R. Zhang, A.J. Stacy, M. Luderer, G.M. Lanza, L.V. Wang, A green synthesis of carbon nanoparticles from honey and their use in real-time photoacoustic imaging, Nano research 6(5) (2013) 312-325
A. Shukla-Dave, H. Hricak, Role of MRI in prostate cancer detection, NMR in Biomedicine 27(1) (2014) 16-24
N. Gong, H. Wang, S. Li, Y. Deng, X.a. Chen, L. Ye, W. Gu, Microwave-assisted polyol synthesis of gadolinium-doped green luminescent carbon dots as a bimodal nanoprobe, Langmuir 30(36) (2014) 10933-10939
Q . Jia, J. Ge, W. Liu, X. Zheng, S. Chen, Y. Wen, H. Zhang, P. Wang, A magnetofluorescent carbon dot assembly as an acidic H2O2-driven oxygenerator to regulate tumor hypoxia for simultaneous bimodal imaging and enhanced photodynamic therapy, Advanced Materials 30(13) (2018) 1706090
T.S. Atabaev, Z. Piao, A. Molkenova, Carbon dots doped with dysprosium: a bimodal nanoprobe for MRI and fluorescence imaging, Journal of functional biomaterials 9(2) (2018) 35
Y. Su, S. Liu, Y. Guan, Z. Xie, M. Zheng, X. Jing, Renal clearable Hafnium-doped carbon dots for CT/Fluorescence imaging of orthotopic liver cancer, Biomaterials 255 (2020) 120110
H. Su, Y. Liao, F. Wu, X. Sun, H. Liu, K. Wang, X. Zhu, Cetuximab-conjugated iodine doped carbon dots as a dual fluorescent/CT probe for targeted imaging of lung cancer cells, Colloids and Surfaces B: Biointerfaces 170 (2018) 194-200
R. Mohammadinejad, A. Dadashzadeh, S. Moghassemi, M. Ashrafizadeh, A. Dehshahri, A. Pardakhty, H. Sassan, S.-M. Sohrevardi, A. Mandegary, Shedding light on gene therapy: Carbon dots for the minimally invasive image-guided delivery of plasmids and noncoding RNAs-A review, Journal of advanced research 18 (2019) 81-93
B.B. Chen, M.L. Liu, C.Z. Huang, Recent advances of carbon dots in imaging-guided theranostics, TrAC Trends in Analytical Chemistry (2020) 116116
F. Du, L. Zhang, L. Zhang, M. Zhang, A. Gong, Y. Tan, J. Miao, Y. Gong, M. Sun, H. Ju, Engineered gadolinium-doped carbon dots for magnetic resonance imaging-guided radiotherapy of tumors, Biomaterials 121 (2017) 109-120
W. Wang, Q . Zhang, M. Zhang, Y. Liu, J. Shen, N. Zhou, X. Lu, C. Zhao, Multifunctional red carbon dots: a theranostic platform for magnetic resonance imaging and fluorescence imaging-guided chemodynamic therapy, Analyst 145(10) (2020) 3592-3597