Nanotoxicity unveiled: Evaluating exposure risks and assessing the impact of nanoparticles on human health

• This review explores the dual-edged nature of nanotechnology, showcasing its significant health risks to human health and the environment. • It emphasizes how nanoparticles can induce reactive oxygen species, triggering oxidative stress, inflammation, and disturbances in cellular antioxidant defenses. • Fundamental physicochemical properties like size, shape, and surface charge are discussed for their critical role in determining nanoparticle toxicity. • The paper also highlights nanoparticles’ ability to cross physiological barriers, potentially accumulating in various organs and associated toxicities. • This paper discusses various methods for assessing toxicity and examines the current landscape of regulatory efforts surrounding nanotoxicity. Nanomaterials have been widely used across medical and health sciences due to their unique physicochemical characteristics, versatile functionalisation, and remarkable tissue penetration abilities. As nanotechnology continues to evolve, concerns regarding the potential toxicological effects of these materials are growing. Despite their promising biomedical applications, comprehensive safety data remains limited. This review details the physicochemical properties of the nanoparticles contributing to the development of potentially adverse effects on human health and the environment. It explores the cellular and molecular mechanisms through which nanoparticles induce toxicity. It assesses current nanotoxicity evaluation strategies, including in vitro, in vivo, and in silico models, along with supporting methodologies. The review also addresses the regulatory landscape of nanotoxicology, outlining the challenges in developing standardised protocols to ensure the safe and effective use of nanomaterials in the health sector. Factors such as particle size, dosage regimen, surface chemistry, and immunogenic potential of nanomaterials play a pivotal role in nanotoxicity. Nanoparticles may accumulate in diverse tissues, leading to oxidative stress, inflammation, and cellular and mitochondrial DNA damage. While regulatory agencies like the FDA, EMA, and CDE have issued guidelines for the safer use of nanomaterials, a globally harmonised framework is still absent. A deep understanding of nanotoxicity is crucial for the safe and sustainable development of nanomaterials. Future efforts should incorporate artificial intelligence and machine learning to predict, assess, and mitigate nanotoxicity by analysing complex data, identifying patterns, and refining nanoparticle design.