Nano: Mechanism of toxicity
Dr Pawan Kumar (PK) Gupta
President, ASAW; Director, Toxicology; formerly Div Head, IVRI Advisor WHO; Editor/Author/Expert WHO, UNFAO and IAEA
Introduction
In the past decade, the field of nanotechnology has received considerable attention due to its wide variety of applications being extended to the biotechnology, electronics, aerospace, and computer industries. More recently, nanotechnology is also applied to the field of nanomedicine, which covers nanotechnology-based diagnosis, treatment and prevention of human diseases such as cancer, improving human health and well-being. Exposure to nanomaterials (NMs) may be dangerous, the matter of their toxicity in humans is still unresolved. The chapter highlights the mechanism of NM toxicity including pathogenetic pathways, binding to cell exterior, dissolution [when they dissolve in liquid, which releases ions (charged molecules) into the environment] and activated by oxidative and nonoxidative stress leading to cell death. In addition, new insights on the complex molecular interrelationships arising from “omics” in light of the information they can provide on specific intracellular events elicited by NMs have been discussed briefly.
Key points
? NPs have intrinsic toxicity profiles. Properties of NPs that might increase the toxic potential include (1) particle size, (2) surface area and charge, (3) shape/structure, (4) solubility, (5) surface coatings and many others.
? Significance of dose, dose rate, dose metric, and biokinetics are very useful parameters for the safety evaluation of newly engineered NPs.
? Current evidence indicates that the smaller the NPs, the more pronounced their
toxic effects are.
? NPs, due to their small size, can penetrate the finest lung structures by breathing, can cause inflammatory reactions, and subsequently can enter the bloodstream. The circulatory system distributes such particles throughout the body, where they can enter other organs. NPs can also be actively or passively incorporated in cells, and harmful effects cannot be excluded.
? Mechanism of nanotoxicity include; silver NPs (AgNps) are among the most commercialized NPs due to their antimicrobial potential.
? AgNp-based cosmetics, therapeutic agents and household products are in wide use, which raised a public concern regarding their safety associated with human and environmental use.
? Studies have revealed the main cell toxicity mechanism includes nitrogen oxide
(NO) overproduction, effect on pathogenetic pathways, binding to cell exterior,
dissolution [when they dissolve in liquid, which releases ions (charged molecules)
into the environment] and activated by oxidative and nonoxidative stress leading
to cell death.
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? Upon NP exposure, reactive oxygen species (ROS) generation is capable of inducing oxidative DNA damage, strand breaks, protein denaturation, and lipid peroxidation thereby demonstrating the mutagenic and carcinogenic characteristics associated with NP.
? Oxidative stress due to direct generation of ROS at the surface of NPs or indirectly by target cells following internalization of NPs is a common mechanism responsible for the toxicity of engineered NMs.
Further reading
AshaRani, P.V., Prakash, H.M., Valiyaveettil, S., 2009. Anti-proliferative activity of silver nanoparticles. BMC Cell Biol. 10 (65), 114. Available from: https://doi.org/10.1186/1471-2121-10-65.
Available from: https://www.biomedcentral.com/1471-2121/10/65.
Ayd?n, A., Sipahi, H., Charehsaz, M., 2012. NPs toxicity and their routes of exposures. In: Recent Advances in Novel Drug Carrier Systems. Intech Chapter 18, pp. 483-500.
Ayd?n, A., Sipahi, H., Charehsaz, M., 2012. NPs toxicity and their routes of exposures. In: Recent Advances in Novel Drug Carrier Systems. Intech Chapter 18, pp. 483500. Available from: https://doi.org/10.5772/51230
Fr?hlich, E., 2013. Cellular targets and mechanisms in the cytotoxic action of non-biodegradable engineered nanoparticles. Curr. Drug. Metab. 14 (9), 976988. Available from: www.ncbi.nlm.nih.gov/pmc/articles/PMC3822521/.
Gupta, P.K., 2020a. Toxic effects of nanoparticles, Toxicology: Resource for Self Study Questions, second ed. Kinder Direct Publications (Chapter 15).
Gupta, P.K., 2020b. Toxicology of nanomaterial particles, Problem Solving Questions in Toxicology -A Study Guide for the Board and other Examinations, first ed. Springer nature, Switzerland,Chapter 14.
Gupta, P.K., 2020c. Toxic effects of nanoparticles, Brain Storming Questions in Toxicology, first ed. Taylor & Francis Group, LLC. CRC Press, pp. 297300.
Gupta, P.K., 2023. Naotoxicology of nanobiomedicine, first ed. Springer nature, Switzerland
Jaison, J., Barhoum, A., Chan, Y.S., Dufresne, A., et al., 2018. Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein J. Nanotechnol. 9, 10501074.
McShan, D., Ray, P.C., Yu, H., 2014. Molecular toxicity mechanism of nanosilver. J. Food Drug Anal. 22 (1), 116127.
Warheit, D.B., Oberd?rster, G., Kane, A.B., et al., 2019. Nanoparticle toxicology. In: Klaassen, C.D. (Ed.), Casarett and Doull’s Toxicology: The Basic Science of Poisons, nineth ed. McGraw-Hill Education, pp. 13811430.