Nanotoxicology

Question: Write about Nano toxicology including these mechanisms of toxicity Nanomaterial Uptake, Translocation, and Intracellular? Answer: Nanotoxicology is a branch of toxicology/nanotechnology that deals with the study of adverse effects or toxicity of nanomaterials. The term Nanotoxicology was proposed by Donaldson to address the problems likely to be caused by nanoparticles. It includes the study of interactions of nanoparticles with biological systems (cells, fluids and tissues) at nanoscale level (Gallud Fadeel, 2015, 143). On the basis of this interaction, a relationship between physical and chemical properties of nanoparticles can be established which further leads to the induction of toxicological responses. Thus, nanotoxicology helps to understand and assess the possible health risks which are associated with the use of nanoparticles. It has been reported that there are several factors that contribute to toxicological side effects of nanoparticles or nanotoxicity such as the physicochemical properties of nanoparticles, nano particle size, large surface area, flexible structure and chemical composition as well as the shape (Khanna et al., 2015, 1165). Hence, it is important that nanoparticles are evaluated for their toxicity so as to determine whether and to what extent are they posing a threat to human beings and environment. Nanoparticle-associated toxicities results due to changes in the structural and physicochemical properties which leads to changes in biological activities and includes Reactive Oxygen Species (ROS) generation, inflammatory response, oxidative stress, changes in cell signalling and cell function, genetic damage and apoptosis/or necrosis (cell death). The molecular mechanisms behind the toxicity of nanoparticles can be explained as: The uptake of nanomaterials by human beings can occur through several routes such as via respiratory system, circulatory system, central nervous system, gastrointestinal tract, dermal routes and others (inhalation, oral ingestion, injection). For instance, oral ingestion of nanoparticles can lead to their translocation to the central nervous system and hence, these nanoparticles can further accumulate in the brain and can disrupt the normal metabolism ultimately leading to brain toxicity and brain damage. Also, use of cosmetic products that contains nanoparticles for example, sunscreens can lead to dermal exposure and entry of nanoparticles and their further intracellular distribution as well as accumulation in various organs (Khanna et al., 2015, 1166). Nanomaterials can also lead to oxidative stress through production of Reactive Oxygen Species (ROS) and is one of the major causes of nanotoxicity. The induction of Reactive oxygen species by nanomaterials is primarily due to the pre sence of pro-oxidant functional groups on the surface of nanoparticles and due to the interaction between the cell and nanoparticles. The generation of Reactive oxygen species in excess can cause cell damage, DNA damage, chromosomal fragmentation, breakage in DNA strand and genetic mutations (Manke et al., 2013, 7). The induction of ROS response immediately results in activation and initiation of pro-inflammatory responses as well as multiple signalling cascades such as phosphoinositide 3-kinase (PI3-K) pathways, mitogen-activated protein kinase (MAPK) pathways also gets activated. Activation of these pathways leads to the transcription and expression of number of pro-inflammatory genes. Such inflammatory responses further lead to the decrease in the membrane potential of mitochondria and can even lead to the destruction of mitochondria sometimes. Increased levels of lipid peroxide are also observed along with decrease in antioxidant enzyme activities. This alters the normal cell fu nctioning and cell metabolism. This in turn can lead to cell apoptosis and/or cell death (Farhan et al., 2014, 472). Therefore, ROS generation and oxidative stress is one of the primary mechanisms contributing to the toxicity of nanoparticles or nanotoxicity and can act as an inducer for a series of events like inflammation, cell injury, damage to cell membranes and cell organelles as well as DNA, apoptosis/necrosis. However, the exact mechanism behind nanoparticle-mediated toxicity needs to be explored and studied in order to reduce the toxicological side effects of nanomaterials. References Farhan, Mohd., Khan, Imran., and Thiagarajan, Padma. Nanotoxicology and its Implications. Research Journal of Pharmaceutical, Biological and Chemical Sciences 5, no. 1 (2014): 470-479. Gallud, Audrey., and Fadeel, Bengt. Keeping it small: towards a molecular definition of nanotoxicology. European Journal of Nanomedicine 7, no. 3 (2015): 143-151, DOI 10.1515/ejnm-2015-0020. Khanna, Puja., Ong, Cynthia., Bay, Boon Huat., and Baeg, Gyeong Hun. Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death. Nanomaterials 5, (2015): 1163-1180, doi:10.3390/nano5031163. Manke, Amruta., Wang, Liying., and Rojanasakul, Yon. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity. BioMed Research International, (2013): 1-15.