ABSTRACT

Recent developments and technical advances in nanotechnology and nanosciences have given rise to concerns about the possible negative impact of nanomaterials (NMs) on human health and the environment. The increased use of NMs in everyday products and a number of industrial processes exacerbate this worry. Large-scale production of NM-based products and devices is by no means a fantasy, and nanotechnology is already present in myriad household products including textiles, construction materials, electronics, surface coatings, fuels, and solar cells. The application of nanotechnology to the medical field, particularly for the treatment of complex diseases in which conventional medicines lack treatment or diagnostic efficacy, has grown in parallel with industrial use. NMs are rapidly emerging as promising drug delivery vehicles, contrast agents, or scaffolds for tissue engineering.However, the toxicological evaluation of NMs due to either unintended or deliberate exposure is challenging. NMs are complex and variable, and a lack of long-term studies and technical

limitations in tracking and quantifying NMs in organisms and cells hampers progress.Studying the translocation and eventual fate of NMs is fundamental to comprehending possible toxicological mechanisms. The toxicological effects of NMs will depend on a number of different factors, such as the organs that the NMs reach and their dose. Fate and translocation studies are particularly important in medical applications of NMs, in which their capacity to target selected organs and subcellular domains needs to be established.On exposure, NMs can translocate into the body by crossing the epithelial barriers provided by the skin, the gastrointestinal tract, the upper respiratory tract, or the lungs. For medical purposes, NMs may also be administered parenterally or intravenously. Once in the circulatory system, NMs redistribute and must cross an endothelial barrier to translocate into remote tissues or organs. The biokinetics, biodistribution, and tissue and cellular interactions of NMs are complex and are influenced both by the nature of the NMs and their surface functionalisation.NMs eventually gain access to the inside of the cell. In order to understand the biochemical action(s) of NMs, mechanisms of cellular uptake, intracellular localisation, and intracellular processing need to be characterised.