Читать книгу Green Nanomaterials - Siddharth Patwardhan - Страница 24

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].