Figure 2.8. Schematic of the types of sectors and applications in which nanomaterials are used.

2.4.1 Nanomedicine

      Healthcare utilises a range of nanomaterials, such as silver in wound-dressing (covered in later sections on consumer products), however, since the 1980s, and with a rapid increased effort in the last 20 years, a new field of biomedical research and application has developed called nanomedicine. Nanomedicine is the utilisation of nanotechnology in medicine. This is a really powerful concept, due once again to length scale. As can be seen from figure 2.1, medically relevant biological entities such as proteins and DNA are comparably sized to nanoparticles, making their interaction specific and optimal. Nanomedicine has utilised very specific nanoparticles for imaging disease or specific markers in areas of the body (diagnostics/imaging), or for treatment (therapeutics) or in some cases both (theragnostics) for a range of target diseases. This includes using nanoparticles to highlight specific areas of disease, for either imaging or removal (by magnetic separation), using them as vehicles to deliver drugs to specific disease sites, or using their nanoscale properties such as photothermia and magnetic hyperthermia to treat diseases, with an emphasis on cancer [8]. In vitro diagnostic immunoassays will be discussed as the third application, however, the overlapping field of nanomaterials in tissue engineering and regenerative medicine, while fascinating, is too large to topic to discuss here and as such is beyond the scope of this chapter.

      2.4.1.1 Generic biomedical nanoparticle

      When considering applications in vivo there are key factors to consider, the most important being efficacy, toxicity and biocompatibility (the latter two are discussed in section 2.5). These properties along with mode of action can all be controlled via either the particle inorganic core, the coating, or functional biomolecules/small drug molecules that can decorate the exterior. A generic biomedical nanoparticle is shown in figure 2.8(A).

      It should be noted that not all of these three components may be strictly necessary (e.g. due to their inert properties, we will we see gold nanoparticles with no coating etc), and the properties above can be delivered by varying components (e.g. the therapeutic can be an active drug molecule on the surface, or heat treatment from the inorganic core). The inorganic core offers the nanomaterial’s fundamental form. It could be that the particle’s key property is simply to be inert and dense (to aid visualisation), but more commonly, the core offers the unique nanoproperties discussed in section 2.3 which can be utilised in the medical application. The main functions of the coating are: (1) to provide protection (of the particle against degradation from the environment) and (2) to protect the surroundings from toxic effects of the inorganic material. The two are related: the more stable the particle, the less likely it is to dissolve and prove toxic to the body by leakage. The coating is vital for nanomaterials with unstable or toxic cores such as CdSe quantum dots. These are regularly coated with ZnS and then again with an organic coating to prevent toxicity and increase biocompatibility. The second main function is to aid the particle’s biocompatibility. Popular coatings such as dextran are cheap and increase biocompatibility. It is well known that coating with polyethylene glycol (PEG) increases blood circulation times by preventing nanoparticle removal by the immune system. The uptake of modified nanoparticles by cancer cells can be increased by coating in a pH-sensitive zwitterionic coating, that becomes charged at the cancer site (lower pH), so is more readily uptaken, increasing the accumulation at the cancer site [9]. Using biologically derived coatings provides further ‘stealth’ by invading the immune system and targeting cancer sites by disguising the nanoparticle as the immune system, using macrophage membranes as coatings [10]. The final function of the coating is to enable easy attachment of the third component: active biomolecules. This can be achieved through a range of chemistry, mentioned briefly in later sections. Finally, the nanoparticle can be decorated with active biomolecules or small molecular drugs that can be used to target the nanoparticle to the site of the disease, or can be a drug or biological therapies to treat a disease (discussed in more detail in the therapeutics section).

      This field is far-reaching, so to keep the content of this section focused on the types of nanoparticles discussed in later chapters and the properties we have discussed earlier in this chapter, only imaging/diagnostics and therapeutics will be discussed here. This critical area of nanomedicine utilising nanoparticles is still in its infancy, with only a handful of nanomaterial-related nanomedicines being FDA approved so far [11].

      2.4.1.2 Imaging

      There is a vast range of medical imaging techniques with various purposes and advantages. Many (e.g. ultrasound scanning) are not enhanced by inorganic nanomaterials, so will not be discussed further in this section. Some (such as positron emission tomography (PET)) are starting to benefit from enhancement with nanoparticles, but expand into the science of radioisotopes, which again is beyond the scope of this section (see [20] for the development of PET with nanoparticles). Nanomaterials can act as a visualisation probe (highlighting an area of interest) in many microscopy and tomography techniques (see chapter 3 for techniques), or enhance the signal for a specific area, because of its nanoproperties such as nanomagnetism in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). The nanomaterials become diagnostic probes by being decorated with biomarkers such as antibodies that will target individual diseases, thus specifically detecting and emphasising these areas.

      Probes for microscopy can be used both in vitro and in vivo. Gold nanoparticles have been used extensively on both accounts. Gold can be decorated effectively (e.g. with antibodies) by taking advantage of the strong gold–sulphur bond using a cysteine residue which contains a sulphur. Thus, gold nanoparticles coated with cancer-targeting antibodies (e.g. anti-EGFR (epidermal growth factor receptor)) can be used to visualise cancerous cells with optical microscopy in vitro (figure 2.9(Bi)) [12].