Mitigating oxidative stress toxicities of environmental pollutants by antioxidant nanoformulations

Oxidative stress arising from reactive oxygen and nitrogen species (RONS) poses a severe threat to living organisms by causing extensive cellular and subcellular damage. Environmental pollutants (e.g., xenoestrogens, pesticides, heavy metals, and polycyclic aromatic hydrocarbons) urther amplify RONS generation, disrupting mitochondrial function and triggering chronic inflammation. Mitochondrial dysfunction not only hinders energy metabolism but also facilitates the release of pro-apoptotic factors (e.g., cytochrome c), ultimately leading to programmed cell death. Consequently, heightened oxidative stress and mitochondrial impairment are key contributors to a range of chronic illnesses, including metabolic, cardiovascular, endocrine, reproductive, neurodegenerative diseases like Alzheimer’s disease, and cancer. While exogenous antioxidants have shown potential in neutralizing RONS and alleviating oxidative damage, clinical applications are hampered by poor bioavailability, instability, and limited cellular uptake. Antioxidant nanoformulations, particularly those employing biodegradable lipidic and polymeric nanocarriers, offer a promising strategy to address these challenges. Formulated nanoscale delivery systems and bioengineered nanocarriers have been developed for the delivery of antioxidants, which have enhanced antioxidant stability and targeted delivery, and improved therapeutic outcomes. This review discusses the latest advances in nanocarrier-based antioxidant therapies, emphasizing their capacity to mitigate toxicities induced by environmental pollutants and oxidative stress, ultimately opening new prospects for disease management and preventive healthcare. • Environmental pollutants (pesticides, heavy metals) amplify RONS and spark chronic inflammation. • Mitochondrial dysfunction impedes energy metabolism and releases cytochrome c, prompting apoptosis. • Heightened oxidative stress, mitochondrial harm underlie chronic metabolic, neurological diseases. • Standard antioxidants show promise but face poor solubility, instability, and uptake challenges. • Nanocarrier-based antioxidant therapies boost bioavailability, stability, and targeted delivery.