A wide variety of nanomaterials have been used as core materials for the subsequent construction of nanomedical systems. The core material is important in terms of the detection technologies that can be used for diagnostics. The core building blocks of a nanomedical system can have both structural and functional attributes. Structurally, it is a starting point for building multilayered nanomedical systems with a combination of genes or drugs, targeting molecules, and stealth molecules to evade the immune system in vivo. It is also the starting place in the manufacturing process.

Nanomaterials are potentially a nanotoxicity problem. One potential source of nanomaterial toxicity is the large surface-to-volume ratio inherent in materials on the nanoscale size range. Many chemical reactions are aided by surfaces that can bring together different molecules for potential interactions and aid in their reorientations for potential interactions. In this way, small nanoparticles can act as catalysts and like enzymes to amplify the effects of interactions between molecules. Reactivity of nanomaterials also varies widely with size. For all of these reasons, nanotoxicity should be measured using nanoparticles of specific size ranges. The same nanomaterials can be more or less cytotoxic depending on their size. Biocoatings may hide the true nanotoxicity.

This is the only chapter of the book devoted to the characterizations and measurements of the nanoparticles themselves, although it does include material related to the interaction forces between nanoparticles and cells. Zeta potential is probably the most important factor in determining whether nanoparticles will agglomerate in clusters. If you observe agglomeration happening to your nanoparticles (a very common problem), it is likely to be a problem with the zeta potential of your nanoparticles. The focus of the chapter is on the importance of “zeta potential,” which governs the fundamental electrostatic interactions of nanoparticles with each other as well as nanoparticle interactions with cells in an aqueous environment. Zeta potential is perhaps the single most important design consideration of nanomedical systems.

The normal paradigm for developing a new nanomedical system is to start with an in vitro cell line (usually human) system and then progress to excised, or biopsied , tissue from a human (ex vivo). Finally, to better simulate the effects of a total organism, we begin in vivo studies, usually on an animal system. This has been the general paradigm for decades. Now we have new “organ-on-a-chip” in vitro models that generate organ-like human tissue on an in vitro format. There have even been more recent promising efforts at generating “human-on-a-chip” technologies.

“Total design” of nanomedical systems means that you must take a total system-level design approach, but where the order in the design process matters – and each design step affects all preceding and subsequent design steps. The total design concept means that the essence of the design is a multilayered approach corresponding to a multistep targeting and drug delivery process. This chapter teaches how to design integrated nanomedical systems.

While nanomedical system design begins with the choice of core materials, the ultimate usefulness of these nanomedical systems is driven by the subsequent attachment of biomolecules in a series of layers. The initial attachment process (i.e., bioconjugation) requires biomolecules to be attached to a core material that is typically nonorganic and may consist of materials quite foreign to these biomolecules. Attachment strategies of biomolecules to the core depend on the composition of core materials.

As discussed in Chapter 1, unique features of nanomaterials such as size-dependent optical and magnetic properties, and high surface-to-volume ratio make them particularly interesting for applications in electronics and biomedicine. Biomedical applications are a powerful driver of the development of bionano hybrids, and novel preparation strategies have already enabled manufacturing of high-quality nanomaterials such as carbon nanotubes at scales that can satisfy market demands. Although the size of nanomaterials brings numerous advantages, working with them can be challenging. Due to their high surface energy, nanoparticles can form random aggregates, or non-selectively bind various molecular species, which impacts their physiochemical properties. This can be prevented by the functionalisation of nanomaterials’ surface with known molecules in a controllable way. Surface modification not only improves the stability of nanomaterials, but enables introduction of various functional groups that can change their properties and make them more adaptable to a broad range of applications.

Bionanotechnology has the potential not only to improve existing medical processes but also to introduce entirely new tools and materials. Advances have already been made, in particular, in design of probes and biosensors for advanced diagnostics, targeted drug nanocarriers and environment-responsive materials for tissue engineering. We need to keep in mind that at the core of all of these applications is the fundamental question of the nature of the interaction of nanomaterials and nanostructured surfaces with biological systems. The exploration of these interactions is strongly embedded within the field of nanomedicine, but it is also a part of nanotoxicology, a field that studies the environmental impact of new materials. Some strategies, findings and policy actions concerning the regulation of use of nanomaterials will be covered in the last chapter.

Despite the relative youth of the term nanotechnology, as far as we know nanomaterials have been around for centuries. Hundreds of years ago, dispersions of gold and silver nanoparticles were used by master glassblowers to produce coloured decorative glass for church windows (Figure 2.1a) or luxury glassware such as the Lycurgus Cup from fourth century CE Rome (Figure 2.1b). In the late nineteenth and early twentieth centuries, industrialists used carbon black to reinforce rubber and thus improve its strength, tensile properties and tear. We know now that carbon black is made of carbon particles that can vary in size, and some of them are nanosized spheres. But practical uses of early nanotechnology were not constrained only to Europe. A corrosion resistant azure pigment known as Mayan blue, first produced in 800 CE, was discovered in the pre-Columbian Mayan city of Chichen Itza (Figure 2.1c). It is a complex material made of nanoporous clay used to stablise the blue indigo dye. Damascus steel swords made in the Middle East between 300 CE and 1700 CE were known for their impressive strength and exceptionally sharp cutting edge, and studies have shown that the steel contains nanotubes and nanowire structures (Reibold, 2008). Swords were produced in a process of forging and forming that employs coal, iron powder, high temperatures and high pressures applied during hammering, a protocol that is in many ways similar to how the nanotubes are made today (see Section 2.4.2).