Nanotoxicology: Focus on nanomedicine

This chapter reflects the progress made within nanotoxicology research over recent years and discusses how hazard investigations may be better designed to more accurately predict NM toxicity. A focus will be placed on the exploitation of NMs as nanomedicines and the implications of this for nanotoxicology investigations but a number of the issues raised are more widely applicable to other applications of NMs. 36.2 Nanomedicine and NanotoxicologyOne of the most prominent areas of research and interest in NM exploitation is the field of nanomedicine. NMs maybe used as a means of accurate, early diagnosis and effective treatment of disease through the development of novel drug delivery systems, new therapeutics, and diagnostics. Importantly, a diverse array of NMs may be used as delivery agents as they are excellent carriers of therapeutic or diagnostic agents. For example, vesicles, micelles, and polymer particles, as well as metal or metal oxides of various types, have been developed for drug delivery (e.g., [2-4]). Alternatively, NMs themselves may have diagnostic or therapeutic properties that can be exploited in a clinical setting. Some applications include using the same NM for both purposes, such as paramagnetic iron oxide or gold NM, both of which are used as a contrast agent in imaging as well as for photothermal ablation (hyperthermia therapy) within the same patient [5]. The simultaneous diagnosis and treatment of disease is therefore possible through the use of NMs, and the term “theranostics” has

been coined to describe this phenomenon. The use of NMs is anticipated to be extremely advantageous as a means of noninvasive, early diagnostic imaging, which combined with a therapeutic function could revolutionize current medical practice. The continued interest and optimism surrounding the utilization of NMs within medical applications is encouraged by the knowledge that a number of novel NM-based therapeutics are in transition from a research to a clinical phase [6].Despite the diversity of nanomedicines under development, many of these new devices share the same principal structure. Thus, they are typically composed of three components: an NM core, a shell/coating (typically a polymer to improve biocompatibility and stability), and one or more functional moieties on the surface (e.g., targeting ligand, drug) (Fig. 36.1). The intelligent design and precise control of the physicochemical properties of NMs can be used to ensure efficacy, whilst minimizing the likelihood of adverse effects developing. For example, the specific targeting of NMs to their required site of action is essential in order to minimize adverse effects associated with systemic administration, and this can be achieved through passive or active processes. For example, controlling NM size can enable their passive delivery to tumors. Specifically, the fenestrations in tumor capillaries provide a relatively leaky barrier compared to other tissues, and the size of these fenestrations is optimal for the capture of NMs. In addition, modification of NM surface properties using carefully selected targeting moieties can enable the specific delivery of NMs to the required target site. Surface modifications are also routinely used to increase the circulation time of NMs in blood (e.g., polyethylene glycol [PEG]).