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Nanomaterials

This chapter1 is not an exhaustive review of nanomaterials. Its objective is to describe some of the carbon-based and inorganic nanomaterials, frequently used in the design of sensors. Some nanomaterials with opto-electronic properties that have not really been used in the design of sensors but also have specific properties that have led to their application in the biomedical field, in particular in biological imaging, will also be described.

1.1. Carbon nanomaterials

Fullerenes, carbon nanotubes (CNTs), nano-diamonds (NDs) and carbon quantum particles or carbon quantum dots (CQDs) were all discovered before the 2000s, followed by graphene in 2005. Due to their remarkable physicochemical properties, fullerenes, CNTs and graphene (G) have given rise to innumerable applications and their exploitation has remained continuous, but with a much quicker development of G compared to fullerenes and CNTs.

1.1.1. Fullerenes

In 1985, Kroto et al. (1985) discovered Buckminsterfullerene C60 (hereinafter referred to as fullerene C60) and revealed its balloon-shaped structure, consisting of an assembly of sp2 carbon atoms, organized in the form of pentagons (12) and hexagons (20). Fullerene chemistry then developed and gave rise to a multitude of applications, in fields as diverse as electronics, energy, biology and medicine. Along with C60 and C70, the two most stable forms (Figure 1.1), new fullerenes were subsequently synthesized, with more carbon atoms.

1.1.1.1. Electrophilic and antioxidant properties of fullerenes

The electrophilic nature of fullerenes allows the formation of anions with six negative charges, corresponding to the acceptance of six electrons by lower unoccupied molecular orbitals (LUMOs). The progressive electrochemical reduction in six steps of C60 and C70 shows that the six reduction states of fullerene can be obtained with good stability (Xie et al. 1992) (Figure 1.1).

Figure 1.1. (a) Image of fullerene C60. Adapted from Balch et al. (1998). (b) Voltametric redox curves of C60 in solution in an acetonitrile/toluene mixture at low temperature (-10°C). Adapted from Xie et al. (1992).

COMMENT ON FIGURE 1.1.- The red and white symbols (a) represent the C atoms in front and behind the projection plane. The reduction curve obtained by a potential sweep from -0.5 to -3.5 V (blue arrow) clearly shows the six reduction peaks, each corresponding to a gain of one electron. The reverse oxidation curve from -3.5 to -0.5 V (red arrow) shows six oxidation peaks, corresponding to the six intermediate and successive anionic states, thus proving the stability and reversibility of these six redox states. Scan rate: 100 mV/s.

This electronic affinity has been exploited in the fields of medicine and biology. C60 and its derivatives, functionalized by various hydrophilic groups, have been used in the fight against cancer and AIDS (antiretroviral therapy against HIV-1). Functionalized by carbohydrate chains, they have also proven to be good antibacterial agents. Their high affinity for radicals, a property resulting from radical addition to the many fullerene double bonds, means that they are considered as "radical sponges". They are powerful antioxidants, used in biology to neutralize radical oxygen species (ROS), such as the superoxide ion O2-?, hydroxyls HO? or hydrogen peroxide H2O2, particularly impressive regarding DNA and certain proteins. All these properties used for medical purposes have been described in review articles (Bakry et al. 2007; Lalwani and Sitharaman 2013; Acquah et al. 2017; Castro et al. 2017).

1.1.1.2. Chemical reactivity and exofunctionalization

Given their cage-shaped carbon structure, involving only covalent bonds between sp2 carbons, fullerenes are naturally hydrophobic and therefore insoluble in aqueous environments. Their use for biological purposes requires transformations to make them hydrophilic, which is achieved by the grafting of hydroxyl groups (COOH or OH), corresponding to exofunctionalization reactions, typically carried out with C60, and some commercially produced fullerenes (C70, C80, etc.), however at high prices, because of the difficulties in producing them in large quantities (Taylor and Walton 1993; Georgakylas et al. 2015).

Among all the products derived from fullerenes, fullerenols and carboxyfullerenes, obtained by grafting hydroxyl or carboxylic groups onto the surface of fullerenes, have the advantage over simple fullerenes in that they are soluble in aqueous and biological media. This is the case of hexacarboxylated fullerenes (carboxyfullerenes), which are fullerenes with three pairs of carboxylic acids, composed of a mixture of two stereoisomers, C3-C60 and D3-C60 (Figure 1.2)2.

Figure 1.2. Structure of the two stereoisomeric carboxyfullerenes C3-C60 and D3-C60 as per Dugan et al. (1997).

Like simple fullerenes, but with the added advantage of solubility in aqueous media, they have strong antioxidant properties, including the ability to destroy the peroxide ion O2?-, a toxic by-product of cell metabolism. This property makes them very good neuroprotective agents, and research in this area is still ongoing (Dugan et al. 1997; Ali et al. 2004; Gharbi et al. 2005; Ye et al. 2015).

1.1.1.3. Endometallofullerenes (EMFs)

The presence of a cavity allows the encapsulation of chemical species, which is of interest for the design of various markers, used for example in medical imaging. As early as 1985, Smalley et al. identified with mass spectrometry the first fullerene with 60 carbon atoms containing a lanthanum atom (Heath et al. 1985). A few years later, they isolated several metallofullerenes with 60, 70, 74 and 82 carbon atoms, the latter La@C823 being the only one that is stable in contact with air (Chai et al. 1991).

What is remarkable is that for all these new compounds there is no metal release when the compound is placed in a biological medium, which is a considerable improvement compared to metal chelates. This stability is likely due to the transfer of electrons between the La atom and the fullerene, which leads to the ion pair La3+@C823-, and to the fact that fullerene meshes are small enough that they prevent diffusion of the ion La3+ outward.

This discovery, which opened promising prospects in the medical field for diagnostic and therapeutic applications, triggered significant research into the synthesis of new EMFs, with some having applications in cancer therapy. Thus, gadolinium fullerenol Gd@C82(OH)22, initially used as a contrast agent in nuclear magnetic resonance imaging (MRI), also turned out to have a strong anti-cancer activity, different from that of simple fullerene, with low cytotoxicity (Kang et al. 2014)4.

1.1.2. Carbon nanodiamonds (NDs)

Although known since the 1960s5, they only began to be exploited at the end of the 1990s when they were produced by detonation of a mixture of explosive products (trinitrotoluene [TNT] and trinitrobenzene [TNB]) (Greiner et al. 1988). These nanomaterials are now produced commercially. They are used for medical, diagnostic and therapeutic purposes, or to improve the mechanical properties of plastics.

From a mechanical point of view, NDs inherited properties from pure diamonds. They are characterized by their very high hardness and a very high Young's elasticity modulus, making them ideal for use in polishing hard surfaces (ceramics). Their very high chemical stability also allows them to be used in very aggressive environments. Two other particularly interesting properties are their fluorescence and biocompatibility, which make them suitable for biomedical applications (diagnosis and treatment) due to their easy surface functionalization.

Fluorescent nanodiamonds (FNDs) are a new family of nanomaterials, with sizes between 35 and 100 nm (Hsiao et al. 2016) and characterized by the presence of a structural defect inside the crystal (Figure 1.3(a)). This defect, called the nitrogen-vacancy (NV) defect, corresponds to a coupling between a vacancy (absence of a carbon atom in the lattice) and a nitrogen atom, adjacent to the vacancy. It can be easily created by irradiation of NDs crystallites with a helium (He+) or proton (H+)6 ion beam. The processed NDs (equivalent to n-doped NDs) emit stable red fluorescence when excited by a laser. The intensity of the fluorescence depends on the concentration of NVs, which itself is higher the higher the energy of the He+ ion beam used for their manufacture (the concentration of NVs can vary between 10 and 30 ppm in relation to the number of carbon atoms; when unprocessed their concentration is less than 1 ppm)7.

Their biocompatibility, high stability, absence of toxicity as well as their high fluorescence intensity in the red make them diagnostic tools of choice in biology rather than inorganic quantum dots (QDs), which are most often made up of toxic elements Cd, Se, Pb, etc. (Chambers et al. 2008).

Figure 1.3. Fluorescence of ND nanocrystals with NV defects. (a) Structure of an NV defect. (b) Fluorescence spectrum of FNDs (size 35 nm) obtained...