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The research field of nanotechnology promises to deliver copious advantages to the scientific, technological, and industrial divisions, globally. Most notable, and in focus in this chapter, is the contribution of nanotechnology to the medical sector where engineered nanoparticles (ENPs) and nanomaterials (ENMs) can be beneficially applied to monitor, diagnose, and potentially treat human health. Despite heightened interest from industrial and consumer markets pertaining to the significant advantages proposed through ENM medical applications. There remains a substantial concern as to the adverse environmental and human health implications of novel ENMs, particularly within nanomedicine, the clinical application of nanotechnology. Nanotheranostics, now an established science concerned with diagnosing and treating specific adverse human health conditions, utilizes a host of novel ENMs. Initially these ENMs require extensive physicochemical characterization coupled with far-reaching biologically relevant testing encompassing complex in vitro (co-culture) cell models, in vivo and human trials before clinical approval and ultimate use. This chapter will provide an overview of the considerations as to the biocompatibility and toxicological impact of novel nanotheranostics building upon the foundation of metal and carbon-based ENMs as well as quantum dots (QDs) which hold tremendous potential owing to their extremely small size and biological marker capabilities.

Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model. Previous work revealed clear neurotoxic effects of PMA-coated IONPs in distinct cell types that could potentially be applied for nanosafety studies regarding neural cell labeling. Here, we aimed to assess if DMSA-coated IONPs could be regarded as a safer alternative for this purpose and how the cell model impacted our nanosafety optimization study. Hereto, we evaluated cytotoxicity, ROS production, calcium levels, mitochondrial homeostasis and cell morphology in six related neural cell types, namely neural stem cells, an immortalized cell line and a cancer cell line from human and murine origin. The cell lines mostly showed similar responses to both IONPs, which were frequently more pronounced for the PMA-IONPs. Of note, ROS and calcium levels showed opposite trends in the human and murine NSCs, indicating the importance of the species. Indeed, the human cell models were overall more sensitive than their murine counterpart. Despite the clear cell type-specific nanotoxicity profiles, our multiparametric approach revealed that the DMSA-IONPs outperformed the PMA-IONPs in terms of biocompatibility in each cell type. However, major cell type-dependent variations in the observed effects additionally warrant the use of relevant human cell models. Statement of Significance Inorganic nanoparticle (NP) optimization is chiefly performed in vitro. For the optimization of iron oxide (IO)NPs for neural stem cell labeling in the context of regenerative medicine human or rodent neural stem cells, immortalized or cancer cell lines are applied. However, the use of certain cell models can be questioned as they phenotypically differ from the target cell. The impact of the neural cell model on nanosafety remains relatively unexplored. Here we evaluated cell homeostasis upon exposure to PMA- and DMSA-coated IONPs. Of note, the DMSA-IONPs outperformed the PMA-IONPs in each cell type. However, distinct cell type-specific effects were witnessed, indicating that nanosafety should be evaluated in a human cell model that represents the target cell as closely as possible.

Genetic toxicology is the study of chemical and physical perturbations to DNA following exposure to endogenous or exogenous agents. Hazard assessment of engineered nanomaterials involves establishing the ability of these novel materials to induce DNA damage (genotoxicity) and to subsequently initiate tumor formation (carcinogenesis). This chapter explores the current evidence associated with the genotoxic and carcinogenic potential of a range of nanomaterials with commercial applications, including metal, metal oxide, and carbon-based nanomaterials, and the mechanisms involved in the genetic damage. There is increasing evidence supporting the ability of nanomaterials to induce DNA damage through the promotion of oxidative stress, although direct interference with DNA and the cell division machinery has also been observed. The genotoxic potential of nanomaterials clearly depends on the physicochemical properties, but it remains difficult to draw general conclusions. We highlight where further study is required to establish the long-term health effects of nanomaterials.