1.1 Introduction

Carbon is unique among all the elements in the diversity of short-, medium- and long-range configurations it forms with itself and with other elements. Two pure carbon crystalline forms, graphite (sp2, threefold planar bonding) and (cubic) diamond (sp3, fourfold tetrahedral bonding), have been known and utilise by mankind for centuries, along with other less clearly identified carbon materials (coals). Hydrocarbons (oils) and organic materials have also been known for a long time. With the advancement of science and technology at nanoscale, some other forms of carbon such as carbon nanotubes (CNTs), graphene and nanodiamond were discovered and explored. Nanodiamonds are actually carbon nanostructures in which carbon atoms are arranged in diamond-like manner. These structures have been found in different meteorites [1,2,3], proto-planetary nebulae, interplanetary dust [4] and several earth sediments existed since 13,000 years. Although these nanoscale diamond particles were produced, accidentally, several times in 1960s, by Russian scientists, when they were synthesizing diamond from non-diamond carbon using explosion energy [5, 6], but the first formal report on their synthesis was published in the late 1980s [7]. Since then, a lot of work has been reported on synthesis, properties and applications of nanodiamonds.

Nowadays, many techniques are available for the synthesis of nanodiamonds. The nanodiamonds are being synthesized using detonation technique [7], laser assisted synthesis [8], high temperature high pressure (HTHP) high energy ball milling of microcrystalline diamond [9], hydrothermal synthesis [10], chemical vapour deposition (CVD) synthesis [11], ion bombardment on graphite [12], chlorination of carbides [13] and ultrasonic cavitation [14] etc. These methods are entirely different from each other in their mechanisms and choice of precursors. The first three methods i.e. detonation technique, HTHP high energy ball milling and laser assisted synthesis are used for the industrial production of nanodiamonds. Due to its extraordinary properties, nanodiamond can be used for field emission and light emitting applications [15]. Nanodiamond shows high mechanical hardness, inertness and high fracture strength and high surface smoothness, which make it a strong candidate for high-end micro and nanosystems [16]. Fluorescent nanodiamonds are widely being used in bio-imaging as a successful non-toxic replacement of semiconducting nanoparticles and for other medical applications [17,18,19,20]. In addition to this, high reactive surfaces of nanodiamond allow its surface modification easily via chemical approaches and make it suitable for synthesizing high performance composites for various applications [21,22,23,24,25,26,27,28].

1.2 Synthesis of Nanodiamond

1.2.1 Detonation Techniques

Detonation methods are the most popular and widely used methods for the production of nanodiamond. In these methods, energy of explosion is used for the synthesis of nanodiamond. According to the carbon precursor used, detonation technique has three variants.

  1. (i)

    In the first variant, nanodiamond is achieved by the phase transformation of graphite using the energy of shock waves originated by the detonation of explosives. This technique was initially introduced by DeCarli and Jamieson in 1961 and has been used as one of the popular techniques for the synthesis of polycrystalline diamond particles [29]. This technique was later patented by DeCarli in 1966 [30] and, later on, its improved version was patented by Cowan et al. in 1968 [31]. This technique was parallely developed by scientists in former USSR at the VNIITF Institute (Snezhinsk) in the early 1960s but remained in veil because of secrecy [32]. In this method, graphite is filled in a closed chamber, surrounded by the explosives. The whole system is confined in another closed chamber. The detonation of explosives generates high temperature (>2000 K) and high pressure. This high temperature and high pressure is sufficient to transform graphite into micrometre-sized polycrystalline diamond particles. Copper is mixed with graphite to improve the local heating [33].

  2. (ii)

    In the second variant, explosives such as pure Trinitrotoluene (TNT), hexogen, octogen, a mixture of TNT/RDX or a mixture of all or some of these materials with a negative oxygen balance is detonated in a closed chamber. These explosives provide necessary carbon and high energy for the formation of nanocrystalline carbon particles [34]. The closed chamber containing the explosives is usually filled with argon, nitrogen, CO2, hydrogen or water (ice), which act as the coolants. Depending upon the choice of coolant, the processes are called wet or dry processes [35]. In the resultant detonation soot, almost 75% are nanosized diamonds with the average size of 4–5 nm [36]. Due to such small size, nanodiamonds synthesized by detonation are called ultradispersed diamonds or UDD. The amount of nanodiamonds in detonation soot depends upon the coolant used. It has been confirmed that the yield increases in series as hydrogen < argon < nitrogen < CO2. Another controlling factor is the amount of coolant per unit mass of explosives, which determine the inertial pressure of the detonation process. The specific heat of coolant also decides the yield of nanodiamond [37]. This method was developed in former USSR in the early 1960s [32] and further improved subsequently. The ultradispersed nanodiamond produced by this method is also covered by graphite, thus requires purification process. In the purification process, usually mineral acids are used. The purified detonation soot contains around 98% ultradispersed diamond particles of size around 4–5 nm [38].

  3. (iii)

    The third variant of nanodiamond synthesis is less known. It was also invented in former USSR [39]. Various compositions of different explosives can be used in this method and these compositions produce the Nanodiamonds having different structures and sizes. Tatsii et al. [40] analyzed the products obtained by using different explosives/carbon precursor compositions and summarized the results. They used three compositions i.e.; RDX/Carbon Black, RDX/Graphite and Gunpowder/RDX/Graphite and compared the products obtained by these compositions. The detonation pressure measured was 7.5–14.5 GPa. It was observed that the product obtained by the mixture of RDX and carbon black precursor contained cubic nanodiamond particles of average size 20–80 nm while the products obtained by the RDX/Graphite mixture contained microsized particles of mixed crystal structures (diamond, lonsdaleite and graphite). The product extracted from the mixture of Gunpowder, RDX and Graphite contained single-phase particles having homogeneous grain structure with grain size of approximately 1–3 nm. These smaller grains were found to form onion-shaped aggregates [40] (Fig. 1.1).

    Fig. 1.1
    figure 1

    Structure of a single nanodiamond particle, a schematic model illustrating the structure of a single ~5-nm nanodiamond after oxidative purification. The diamond core is covered by a layer of surface functional groups, which stabilize the particle by terminating the dangling bonds. The surface can also be stabilized by the conversion of sp3 carbon to sp2 carbon. A section of the particle has been cut along the amber dashed lines and removed to illustrate the inner diamond structure of the particle. b, c, Close–up views of two regions of the nanodiamond shown in (a). The sp2 carbon (shown in black) forms chains and graphitic patches b the majority of surface atoms are terminated with oxygen-containing groups (c oxygen atoms are shown in red, nitrogen in blue). Some hydrocarbon chains (green, lower left of a, c) and hydrogen terminations (hydrogen atoms are shown in white) are also seen (d). Each nanodiamond is made up of a highly ordered diamond core. Some nanodiamonds are faceted, such as the one shown in this transmission electron micrograph, whereas most have a rounded shape, as shown in (a). The inset is a fast Fourier transform of the micrograph, which confirms that this nanodiamond has a highly ordered diamond core (Reprinted with permission from [5])

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The growth mechanism for the synthesis of nanodiamond via detonation technique can be understood by the phase diagram of carbon (Fig. 1.2) [5]. From the phase diagram, it is evident that the most stable form of carbon is graphite at low pressure, while at high pressure, diamond is the most stable form. Both the graphite and diamond transforms into liquid at the temperature higher than 4500 °C. The diamond-liquid transition temperature is less in the case of nanosized diamond particles and the stability shifted to higher pressures. The detonation (pressure and temperature at Jouguet point (point A in Fig. 1.2)) does not provide enough high pressure and temperature which is required for the formation of bulk liquid, rather it transforms carbon into nanosized liquid droplets of size 1–2 nm. When the pressure and temperature is reduced along the isentrope (red line), these liquid droplets further condense and crystallize into nanodiamond particles [41,42,43,44,45,46,47,48,49,50]. Figure 1.3 shows different stages of nanocarbon formation in detonation technique. Region (I) corresponds to the zone of explosion, the region (II) is the zone of chemical decomposition of explosives (in case explosives are present as the precursors), the region (III) corresponds to Chapman-Jouguet plane (where pressure and Temperature correspond to point A in Fig. 1.2),the region (IV) is the region of expansion of detonation products, the zone (V) is the region of formation of nanosized carbon clusters, zone (VI) is the region of coagulation into nanosized liquid diamond droplets and region (VII) is the region where nanodiamond particles crystallize and grow.

Fig. 1.2
figure 2

Phase diagram of carbon (Reprinted with permission from [5])

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Fig. 1.3
figure 3

Different stages of nanodiamond synthesis by detonation (Reprinted with permission from [5])

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Detonation methods are well established methods for the synthesis of nanodiamonds. Recently, some reports have been published on the modified detonation synthesis of nanodiamonds. Pichot et al. [51] reported the synthesis of ultrasmall nanodiamonds by the explosion of nanosized explosives. For the synthesis of nanosized explosives, they used spray flash-evaporation process. Using this new approach, they were able to synthesize nanodiamonds having average size of 2.8 nm (Fig. 1.4). Nanodiamond particles synthesized by detonation usually contain hydrogen. In their study, Batsanov et al. [52] chose benzotrifuroxan (BTF) as the required explosive for the detonation synthesis of nanodiamonds. The nanodiamond particles obtained by this process were free from hydrogen impurities (Fig. 1.5).

Fig. 1.4
figure 4

TEM image of ultra small nanodiamonds synthesized using detonation of nanosized explosives (Reprinted with permission from [51])

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Fig. 1.5
figure 5

TEM images of hydrogen-free nanodiamond particles synthesized from benzotrifuroxan (BTF) [52]

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1.2.2 Synthesis of Nanodiamond by CVD

Chemical vapour deposition method is one of the most popular methods used for the synthesis of films of carbon nanostructures such as carbon nanotubes [53], graphene [54] and nanodiamonds [55]. In this method, cabonaceous precursors are used in the gaseous form for the deposition of nanodiamond films. The use of chemical vapour deposition for the synthesis of diamond dates back to 1956 when diamond films were produced using precursor mixture containing hydrogen [56]. This method was patented in 1967. Diamonds films were further reported to be synthesized using HF-CVD [57], Microwave assisted CVD [58] and radio plasma enhanced CVD [59] by Japanese researchers. In 1989, Frenklach et al. [60] produced nanodiamond powder in gas phase using microwave CVD employing different hydrocarbons diluted in the mixture of oxygen, hydrogen and argon as the precursors. By this process, diamond nanocrystals of average size around 50 nm were produced. In another study, Frenklach et al. [61] demonstrated the formation of nanodiamond particles of size ranging from 5 nm to several hundred nm, induced by the addition of diborane (B2H6). These methods involve the generation of nanodiamond from activated gaseous phase and used to understand the formation of nanodiamond particles present in space dust. Other methods such as laser induced CVD synthesis of nanodiamond using methane precursor at high temperature and high pressure [62] and microwave plasma torch system using methane with Ar and nitrogen were reported. Recently, there have been several reports published on the improved CVD synthesis of nanodiamond. Park et al. [63] demonstrated the synthesis of nanodiamond using hot filament CVD reactor (Fig. 1.6).

Fig. 1.6
figure 6

Schematic diagram of hot filament reactor used for the synthesis of nanodiamond (Reprinted with permission from [63])

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They observed that the size of single crystalline nanodiamond particles formed by this method lying between 4 and 6 nm, which increased with the capture time. (Fig. 1.7). They did not find other allotropes of carbon, such as graphite or amorphous carbon with nanodiamonds.

Fig. 1.7
figure 7

STEM images of CVD processed nanodiamonds obtained with increasing capture time from left to right (Reprinted with permission from [63])

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1.2.3 High Energy Milling of Microsized Diamond Particles

Nanodiamond can be obtained by high energy milling of microsized diamond particles. Usually, these nanosized diamond particles have haphazard shape which resemble with the smashed glass [64], but in the year 2009, Boudou et al. [9] synthesized quasi-spherical nanosized diamond particles of size below 10 nm. Boudou et al. [65] synthesized uniform nanodiamonds using nitrogen jet milling followed by bead milling of microcrystalline diamond powder. They further purified and sorted out the product obtained by this process to get nanodiamond particles of size below 10 nm. In 2015, Boudou et al. [66] were granted a patent on the process of cubic nanodiamond synthesis using nitrogen jet ball milling. Their process involved the nitrogen jet milling of microcrystalline diamonds followed by the nanomilling using tungsten carbide ball mill. A subsequent acid treatment was used to get rid of unnecessary traces of tungsten carbide powder. After the centrifugation, they obtained round shaped cubic nanocrystalline diamond particles of less than 10 nm (Fig. 1.8).

Fig. 1.8
figure 8

TEM image of diamond nanoparticles prepared by milling of microcrystalline diamonds (Reprinted with permission from [65])

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1.2.4 Laser Assisted Synthesis of Nanodiamond

Laser assisted synthesis is relatively new technique for the synthesis of nanostructures [67]. Nanostructures prepared by chemical methods contain different chemical impurities. Additional purification steps are required to remove these impurities. These purification steps increase the complexity of these processes. Laser ablation is a process in which high energy of laser radiation is used to synthesize high purity nanostructures that do not need any subsequent purification process (Fig. 1.9).

Fig. 1.9
figure 9

Schematic of laser ablation setup used for the synthesis of nanomaterials (Courtesy www.understaiulingnano.com)

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In 2005, Wang et al. [68] presented a detailed analysis of nanocrystal nucleation and growth in liquid medium using laser ablation taking nanodiamond as specific example. They proposed that the synthesis of nanodiamond by laser ablation in liquid medium takes place in following steps (Fig. 1.10).

Fig. 1.10
figure 10

Schematic diagram of the formation of nanodiamond by laser ablation in liquid medium; a formation of high pressure high temperature plume; b formation of diamond nuclei; c formation of diamond nanocrystals (Reproduced with permission from [65])

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  • Formation of plasma plume of carbon atoms with peak pressure and temperature of 15 GPa and 5000 K, respectively (Fig. 1.10a).

  • Steady nucleation of carbon clusters from the carbon atoms due to condensation of plasma as the temperature and pressure drop down from the peak values. This nucleation process continues until the size of these clusters reach the critical nucleation size of diamond (Fig. 1.10b).

  • With the steady nucleation, diamond nuclei are formed followed by the synthesis of diamond crystals. After some time, the growth of nanodiamond seizes due to further decrease in temperature and pressure (Fig. 1.10c).

Yang et al. [69] synthesized diamond nanocrystals using pulsed laser ablation of graphite in liquid medium (Fig. 1.11). They reported that the size of the nanocrystalline diamonds increases with increase in reaction time.

Fig. 1.11
figure 11

TEM images of diamond nanocrystals synthesized using pulsed laser ablation of graphite with different reaction tune of a 1/2 h b 1 h (Reprinted with permission from [69])

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Tarasenkha et al. [70] reported the one step synthesis of nanodiamond by laser ablation of graphite in liquid medium. They obtained different carbon nanostructures using different solvents. Nanodiammond particles were formed by using aqueous diethylenetriaminepentaacetic acid [DTPA] solution as the liquid medium. Gorrini et al. [71] synthesized nanodiamond by laser ablation of graphite dispersed in aqueous medium. Further, they argued that the water acts as a confining medium which is essential for typical confined pulse laser ablation (CPLA) process. They further stated that high pressure and high temperature condition provided by the laser irradiation fall in the liquid region of carbon phase diagram and induces phase change of graphite into liquid carbon. The melted carbon cools immediately due to its contact with the bulk graphite and liquid. The cooling of melted carbon favours the nucleation of diamond phase. In a review article published in 2017, Amans et al. [72] reviewed the reports published on the synthesis of carbon allotropes using laser ablation in liquid medium. They concluded that different carbon nanostructures including nanodiamond can be produced using laser ablation in liquid medium.

1.2.5 Synthesis of Nanodiamonds Using High Energy Particles Irradiation

High energy particle radiation can also be used for the formation of nanodiamond. Banhart et al. [73] used an unconventional method for the synthesis of nanodiamond. They used high energy electron beam to compress the layers of carbon onions towards the centres. This compression allows the conversion of their cores into nanodiamonds. On the other hand, Wesolowski et al. [74] synthesized nanodiamond using the same procedure with minor modification. They used Ne+ ion radiation to convert graphitic onion cores into nanodiamonds. Higher energy transfer, higher beam current, higher displacement cross section due to high energy ion irradiation induced the formation of higher nanodiamond yield in comparison with that in the case of high energy electron radiation. Daulton et al. [75] used high energy Kr+ ions to produce nanodiamond particles inside graphite. In another report published in 2001, Meguru et al. [76] synthesized nanodiamond using irradiation of highly charged ions on highly oriented pyrolytic graphite followed by the surface treatment either by the electron injection from scanning electron microscope or by laser irradiation with He–Cd laser. They reported that the one-time impact of highly charged ion produces one nanodiamond particle without creating any defect in the area surrounding the region of direct impact.

Fig. 1.12
figure 12

Electron diffraction patterns of solid carbon species obtained by ultrasound cavitation; left side diffraction patterns represent the diamond phase while the right side diffraction patterns represent the graphite phase (Reprinted with permission from [14])

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1.2.6 Ultrasound Assisted Synthesis of Nanodiamonds

Synthesis of nanodiamond requires appropriate temperature and pressure conditions. These temperature and pressure conditions may be obtained by ultrasound cavitation. Ultrasound cavitation bubbles are generated in liquid medium. These ultrasonic bubbles collapse and generate a relatively bigger cavity. The temperature and pressure inside the cavity reach at the high values which are required for the formation of nanodiamond under suitable experimental conditions [77] (Fig. 1.12).

Galimov et al. [14] explored the possibility of synthesis of nanodiamond by ultrasound cavitation of hydrocarbon liquid. They used benzene as the working liquid. The ultrasound cavitation in benzene resulted in the synthesis of organic polymers and solid carbon particles. Their experimental investigations suggest that these solid carbon particles consist of nanodiamond particles (Fig. 1.14).

1.2.7 Synthesis of Nanodiamonds Using Carbides

Selective etching of carbides in the presence of etchant gases gives rise to the synthesis of different carbon allotropes including nanocrystalline diamond. Gogotsi et al. [78] demonstrated the synthesis of nano and microcrystalline diamond using silicon carbide at the relatively low temperature about 1000 °C. In their experiment, silicon carbide was exposed to the mixture of chlorine, hydrogen and argon gases in appropriate ratio. Chlorine reacts with Si present in silicon carbide to form SiCl4 as it is thermodynamically more stable than CCl4. In this way, chlorine present in the gaseous mixture selectively etches Si from SiC leaving carbon on SiC substrate. Gogotsi et al. [78] argued that these carbon films have the diamond structure when the etching mixture contains the Cl2/H2 ratio more than or equal to 2:1 and the temperature of about 1000 °C. Some other workers also reported the synthesis of nanodiamond by selective etching of silicon carbide using fluorocarbon plasma [79] and bombardment with hydrogen or carbon ion [80, 81].

1.3 Applications of Nanodiamonds

1.3.1 Polishing and Lubrication

The most basic feature of diamond is its structure in which sp3 hybridized carbon atoms are arranged in tetragonal arrangement. Dense packing and stable hybridization make diamond incredibly strong and hard material [82]. Because of extraordinary hardness, diamond is used in polishing applications since long [64]. For ultrafine polishing, abrasive materials with sub-100 nm grain size are ideal. Because of sub-100 nm size and extraordinary hardness, nanodiamonds are used in fine polishing applications with the finishing better than 4 Å. Liu et al. [83] used nanodiamond suspensions for the polishing of glass ceramics. The polishing of glass ceramics is difficult due to their inconsistency. In their study, Liu et al. used the suspension of nanodiamond particles having different sizes. They found that the suspension of nanodiamonds of average size 54.9 nm performed with highest removal rate and better surface roughness. A superior surface roughness of 0.208 nm was achieved. Usually nanodiamonds are made up of nanosized diamond core and with the graphite existed on the surface [5]. This unique feature makes nanodiamond an attractive lubrication agent. It is assumed that the graphite present at the surface of nanodiamond provides lubrication and its core reduces friction by polishing away the surface roughness. However, purified nanodiamonds were also observed to enhance the lubricantion properties when it is used in grease or oil with PTFE or metal nanoparticles [84]. It is well established that the mechanism of lubrication for nanodiamond is different for different systems. When, it is used in carbon steel system, nanodiamond gets embedded into carbon steel from the lubricant reducing the friction and wear. The wear mechanism is dominated by the viscosity of nanodiamond suspension when it is used for aluminium. Shirwani et al. [85] numerically analyzed the ability of detonation-synthesized nanodiamonds to improve the lubrication and reduce friction in elastohydrodynamic lubrication. Due to the increase in the viscosity of the lubricant in the EHL contact zone, diamond nanoparticles in the lubricant polish the surfaces at the nanoscale which decreases the composite roughness of the contacting surfaces. The reduced composite roughness results in an increased film thickness ratio which yields lower friction. Wang et al. [85] filed a patent describing the method of chemical mechanical planarization of GaN using a chemical mechanical polishing slurry containing ultradispersed diamonds sized below 10 nm suspended in water with a complexing and a passivating agent. Although the exact mechanism behind the improvement of lubrication by addition of nanodiamonds is not completely known, it is a well proven lubrication additive. A detailed study is needed to understand the mechanism of lubrication improvement using nanodiamond. It will be helpful to engineer more efficient lubrication systems.

1.3.2 Nanodiamond Nanocomposites

Extraordinary mechanical hardness, stability and thermal properties of nanodiamond enable them to be used as the filler materials in different composite systems [5]. Nanodiamond has been proved to enhance the adhesive properties [86], electromagnetic shielding properties [87], wear resistance [88], mechanical strength [89,90,91] and thermal conductivity [89, 92] of polymers when used as the filler material in the matrix of polymers. Recently, Zhang et al. [93] prepared a composite using biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC). They modified the original hydrophobic surface of nanodiamonds to be amphipathic with phospholipid. The filling of 10% NDPC into PLGA significantly improved the mechanical properties of PLGA. Nanodiamonds have also been used with other filler materials in polymers matrix. Zhang et al. [94] used nanodiamond nanocluster-decorated graphene oxide as filler material to improve the mechanical strength of epoxy. They observed that epoxy samples containing 0.1% hybrid filler material showed high mechanical stability in comparison with the epoxy composite containing 0.2% filler material. The epoxy composite prepared by ND/GO filler material also exhibited enhanced thermal properties such as decomposition temperature and activation energy. The authors argued that the presence of nanodiamonds not only prevented the agglomeration of GO sheets but also acted as the pinning agent in polymer composite which significantly enhanced the fracture toughness. Choi et al. [95] prepared a nanodiamond grafted nylolon 6,6 (PA66) reinforced PA66 nanocomposites. The tensile strength of this composite increased by 11% and 20.8%, respectively. Even PA66/pristine ND composite showed higher mechanical properties. Kausar [96] synthesized waterborne polyurethane composites with increased thermal properties and observed that the thermal stability of waterborne polyurethane increased significantly after the reinforcement. Vesna et al. [97] prepared Poly(ethylene terephthalate) composite with 1% nanodiamond terminated with carboxylic group and nanodiamond/0.3% graphene platelets by simple melt blending for radiation resistance. They observed that composites with nanodiamond-graphene hybrid filler exhibited high radiation resistivity. Nanodiamond has also been used with different metal and metallic systems to improve different properties of nanocomposites. Neito et al. [98] synthesized WC-ND nanocomposites using thermal spray method. They observed that the addition of nanodiamonds enhances the wear performance. The wear resistance was found to be increased at room temperature, while they observed poor wear resistance at 300 °C. They attributed the decrease in wear resistance at 300 °C to the degradation of carbon phase at this temperature. Yin et al. [99] produced nanodiamond reinforced copper matrix composite film on aluminium alloy substrate using cold spray. They observed that the composites exhibited excellent wear resistance properties. Murugesan et al. [100] presented a concept of novel Ni–B–ND coating for increasing the lifetime of gas and oil equipment. Ni is an excellent coating material and is used to increase the corrosion, abrasion and wear resistance. Boron was introduced in Ni matrix to improve the corrosion resistance of the coating. The addition of ND enhanced the wear behaviour of the coating without affecting its corrosion resistance properties. This relatively new concept has the promise to improve the lifetime of oil and gas equipments. Nanodiamond has been proven to increase the mechanical and thermal properties of different matrices. Therefore, ND reinforced nanocomposites have the potential to be used in different applications. Although nanodiamond reinforced composites have been studied since long, their excellent properties and wide range of applications are continuously adding fuel to the research and development in this area.

1.3.3 Bio-medical Applications

Targeted drug delivery is one the most widely researched and promising topic of research. Different nanomaterials have been tested to act as the drug carrier in targeted drug delivery systems. The main attributes of the material to be used as drug carriers include biocompatibility, ability to carry wide range of drugs, scalability and dispersibility in water [82]. The excellent bio-imaging properties make nanodiamond an excellent drug carrier. Nanodiamond has been demonstrated to be used to carry Doxorubicin (DOX) [101]. Doxorubicin complexes are drugs which are used to treat a wide range of cancers. Chow et al. [102] demonstrated that nanodiamond-DOX complexes can be efficiently used to treat drug resistant breast and liver cancer. The effectiveness of DOX complex-nanodiamond was found to be 10 times more effective than Doxorubicin alone. Nanodiamond can also be used to increase the dispersibility of various drugs which are insoluble in water [103]. In their study, Chen et al. [104] argued that carboxyl groups functionalized nanodiamond particles absorb drug molecules via physisorption or electrostatic interaction. In this way, these molecules may be dispersed in aqueous solution. Using this procedure, several poor water soluble drugs have been dispersed. These drugs include purvalanol A (used in liver cancer treatment), 4-hydroxytamoxifen (used in breast cancer therapy) and dexamethasone (for anti-inflammation) [105]. In another study, Sorafenib, a potential drug to be used in gastric cancer therapy, is mixed with nanodiamonds to form clusters. These clusters were then coated with an amphiphilic lipid, distearoylphosphatidylethanolamine–poly(ethylene glycol) (DSPE–PEG), and tested at mice as animal model. Sorafenib delivered by this procedure was observed to be more effective than it was delivered alone. The Sorafenib-ND clusters coated with DSPE–PEG also reduced metastatic nodules in mice’s liver and kidneys which are responsible for 90% cancer-related deaths [106] (Fig. 1.13).

Fig. 1.13
figure 13

a Illustration of the preparation of lipid-coated diamond nanoparticle clusters loaded with water insoluble sorafenib. b–d Tumour growth inhibition effects m BGC-823 gastric cancer cells induced tumour xenograft mice (20 mg kg−1). b The relative tumour volumes in tumour xenograft models treated with saline, sorafenib suspension, nanodiamond (ND) + sorafenib (Sora) and lipid-coated diamond nanoclusters loaded with sorafenib (SND) by oral gavage (20 mgkg-1). c The photographs of tumours from each group excised on day 23 after oral administration. d The relative tumour weight in mice with treatment of sorafenib, ND + Sora and SND in comparison with saline group. e and f Therapeutic efficacy of SND on suppressing the distant metastasis to liver (e) and kidney (f) in BGC-823 gastric cancer cells induced tumour xenograft mice. Mice were daily treated with saline, sorafenib suspension, ND + Sora and SND at 20 mg kg-1 of sorafenib by oral gavage. At the end point, the visually detected metastatic nodules in each tissue of liver and kidney were counted (Reprinted with permission from [103])

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On the other hand, nanodiamonds can be used to deliver more than one drug at a time. Wang et al. [107] showed that the combination of nanodiamond–DOX, nanodiamond–mitoxantrone, nanodiamond–bleomycin and free paclitaxel can be used efficiently to treat breast cancer.

In other experiment, nanodiamond was used to make vascular barrier leaky, which helped DOX to penetrate the vascular barrier. Therefore, nanodiamond indirectly helped DOX to be delivered. In this study, –NH2 modified nanodiamond was proven to be more effective for vascular barrier leaky [108].

Gene therapy is one of the modern methods to treat different deceases. In these methods, DNA or siRNA is transported to the cytoplasm or nuclei of the cell. Various methods have been developed so far, for the delivery of genes [109,110,111,112]. In their study, Zhang et al. modified nanodiamond with polyethyleneimine and used it for the delivery of DNA. They found 70% increase in performance as compared to that of polyethyleneimine alone [113]. Chen et al. [114] demonstrated the ability of nanodiamond to act as a carrier for the delivery of small interfering RNA (siRNA). siRNA has significant therapeutic properties and a number of carriers exist for their delivery but their biocompatibility is not up to mark. Nanodiamond presents an excellent platform for siRNA delivery. In their another report, Zhang et al. [115] used fluorescent nanodiamonds (FCN) for targeting siRNA to down regulate the expression of polo-like kinase-1 (Plk1) which is a master regulator of mitosis. The amount of FCN required for this process was 1/30 times of the amount of gold nanoparticles earlier used for this purpose. Alwani et al. [116] examined the gene targeting properties of lysine-functionalized nanodiamonds. They observed that lysine functionalization of nanodiamonds improved the dispersivity and stability of nanodiamond-gene complex. Gene therapy is an emerging field which has the promise of treating complex diseases such as genetic disorders and different types of cancers. Extensive research work is needed for the development of therapeutic agents and their delivery platforms. Nanodiamond with appropriate functionalization have been proven as the promising material for targeted delivery of these therapeutic agents.

1.4 Nitrogen Vacancy Centers (NV Centres) in Nanodiamonds and Their Applications in Bio-imaging

Nitrogen vacancy (NV) center is a type of point defect present in diamond lattice. NV centre is composed of one substitutional nitrogen atom bounded with a lattice vacancy [117] (Fig. 1.14). These nitrogen vacancy centres act as the luminescent colour centres. The NV centres absorb in the wavelength range of 460–600 nm. Diamond nanoparticles emit radiation ranging from 550 to 800 nm, when excited by green light [104].

Fig. 1.14
figure 14

A typical structure of NV centre in nanodiamond. The substituted nitrogen atom (blue) is bound to a vacancy (white) in diamond lattice (Reprinted with permission from [117])

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In the nanodiamonds having negligible concentration of nitrogen, these nitrogen defects are created by the implantation of N+ ion followed by the annealing procedure. While, in nanodiamond having substantial amount of nitrogen impurities, the NV centres are created by the electrons or high energy radiation, followed by annealing [104]. Some other processes have also been reported for the production of nitrogen vacancies in nanodiamonds. In the process reported by Baranov et al. [118], the NV centres (with high concentration 1 NV centre per nm3) in nanodiamonds are created by HPHT sintering of nanodiamonds.

These NV centres are classified into two categories i.e. negative NV centres (NV−) and neutral NV centres (NV0). Neutral NV centres have single unpaired electron while, a negative NV vacancy has two unpaired electrons. Therefore, negative NV centres have integer spin (S = 1) and the electronic states associated with these vacancies have triplet ground and excited levels. The triplet levels correspond to three different values of ms spin states of −1, 0 and +1. In the absence of magnetic field, ground state corresponds to two degenerate states (for ms = +1 and −1) and one state for ms = 0. Upon excitation, the electrons are excited from triplet ground state to triplet excited state. During the transition between triplet ground level and triplet excited level, the spins are conserved. Occasionally, non-radiative transitions occur from triplet exited state to singlet metastable state and then electrons return from metastable state to ground state through non-radiative transition [1]. ms = ±1 levels have the higher probability to undertake this type of inter-system crossing. When external resonant magnetic field is applied, the electrons make transition from m = 0 sublevel to m = ±1 sublevel in the ground state. This leads to 30% decrease of fluorescence emission intensity because, from excited m = ±1 level, the preferred transitions are non-radiative. So, the spin states present in NV centres can be determined by measuring the fluorescence variations under resonant magnetic field. This process is typically called the optically detected magnetic resonance (ODMR) [117] (Fig. 1.15).

Fig. 1.15
figure 15

Energy level structure of NV defect and the spin sublevels, optical excitation at 532 nm (green arrow), Fluorescence emission (red arrows 637–750 nm) non-radiative decay processes (black dashed lines) and spin transitions driven by MW fields (Orange lines) (Reprinted with permission from [117])

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The sensitivity of spin states of nanodiamonds with respect to external magnetic field is particularly useful in magnetic resonance imaging (MRI) and optically detected magnetic resonance imaging (ODMRI) of different species particularly, the biomolecules. Use of nanodiamonds in MRI drastically enhances the resolution of MRI [104]. Grinolds et al. [119] demonstrated the very first 3-D spatial mapping technique to sense the dark electronic spins on and near the nanodiamond surface with high resolution. They also employed nanodiamond to sense nuclear spins, whose magnetic moments are 600 times smaller than that of electrons. McGuinness et al. [120] demonstrated the detection of single nanodiamond particle within HeLa cell via probing its magnetic resonance. Nanodiamond-assisted MRI has also been used to imaging and sensing of biomolecules [121,122,123]. ODMRI has also been employed to probe the external parameters that can affect the spin states of NV− vacancies. Kucsko et al. [124] demonstrated the ability to monitor local temperature variations in a living human embryonic fibroblast using nanodiamonds as probes.

The negative NV centres possess strong excitation and emission at 560 and 700 nm, respectively. The absorption cross section of negative NV centre at this wavelength range is 5 × 10−17 cm2, which is comparable to that of dye molecule [104, 125, 126]. On the other hand, the fluorescence decay lifetime of negative NV centre has two components, i.e. one faster component of 1.7 ns and the other slower component of 17 ns. The latter value is beneficial for isolating the emission of nanodiamonds from background signals [104] during fluorescent imaging. Due to extraordinary fluorescence properties and biocompatibility, nanodiamonds have been used for fluorescent imaging of biomolecules and biospecies. In their report, Chen et al. [127] demonstrated the monitoring of the movement of individual nanodiamond within living HeLa cell up to 200 s. Epperla et al. [130] employed diamond nanoparticles as fluorescent trackers to monitor the intracellular transport of proteins through tunnelling membrane nanotubes. Bovine serum albumin (BSA) and green fluorescent protein (GFP) were coated on diamond nanoparticles of approximately 100 nm in diameter by means of physical adsorption. The motion of the protein-decorated diamond nanoparticles through the tunnelling nanotubes could be continuously monitored for longer than 10 min. These studies and some other recent studies [128, 129] suggest that the nanodiamonds can be used in in vivo bio-imaging and as biomarkers. Biocompatibility and extraordinary spin and fluorescent behaviour of nanodiamonds make them a promising material to be used in advanced bio-imaging. Several research groups are working in this area, and it is expected that the world will see many extraordinary applications of nanodiamonds in the field of bio-imaging especially in vivo bio-imaging which is an important aspect of targeted drug delivery.

1.5 Conclusion

As the other allotrope of carbon, nanodiamond also has various extraordinary properties. Due to these extraordinary properties, nanodiamond has remained in the focus of researchers working in the field of nanotechnology and its applications. There are several well established methods of nanodiamond synthesis such as detonation synthesis, and CVD. Recently, some new techniques and procedures, such as laser ablation, for the synthesis of nanodiamonds have been developed. These newly developed methods have the advantage of high purity over the traditional methods. As these newly methods are not cost effective, there is a need of the development of cost effective methods that can deliver high purity nanodiamonds. Nanodiamonds have been exploited to act as the promising material for a number of applications. Some traditional applications of diamond, such as polishing and lubrication, have been improved by the use of nanodiamonds while some new applications have been emerged due to interesting properties of nanodiamonds, which arise due to size reduction. These new applications particularly involved the applications of nanodiamonds in the field of drug delivery and in vivo bio-imaging. Some recent studies proved that the nanodiamond is one of the fastest emerging materials in the field of drug delivery, bio-imaging and bio-marking. There is a need of more intense research to understand the ethical and compatibility related aspects related to the use of nanodiamonds in human disease management.